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52. African Americans With p161 and p162 Oropharyngeal Squamous Cell Carcinomas Have Distinctly Poor Treatment Outcomes Independent of Medical Care Access.

Author

Quinn O’Neill, W., Wasman, Jay, Thuener, Jason, Chatfield-Reed, Kate, Lukesic, Lizabeth, Kyasram, Ravi, Shanahan, John, Szelesety, Blake, Vu, Brandon, Lavertu, Pierre, Rezaee, Rod, Li, Shawn, Fowler, Nicole, Teknos, Theodoros N., and Pan, Quintin

Subjects
PAPILLOMAVIRUSES, BIOMARKERS, HEALTH services accessibility, CONFIDENCE intervals, BLACK people, LOG-rank test, MULTIVARIATE analysis, OROPHARYNGEAL cancer, HEALTH status indicators, TREATMENT delay (Medicine), DESCRIPTIVE statistics, SQUAMOUS cell carcinoma, PROPORTIONAL hazards models
Abstract

PURPOSE Human papilloma virus–positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), diagnosed with p16 immunohistochemistry, is associated with favorable prognosis; however, this connection was established using European American (EA)–skewed populations. The impact of p16/human papillomavirus status on outcomes in African American (AA) OPSCC patients remains to be settled. In this study, we determine the association between cancer disparity and p16 status in an OPSCC cohort controlling for time to treatment initiation (TTI), a surrogate for medical care access. MATERIALS AND METHODS We analyzed data from all patients diagnosed with OPSCC (N = 440) between 2010 and 2017, who received treatment at our academic medical center. Associations between age, disease stage, sex, p16 status, race, TTI, and overall survival (OS) were investigated. RESULTS TTI was similar between AA and EA OPSCC patients in our p161 (P= .291) or p162 (P = .715) cohorts. Among p16+ OPSCC patients, the median OS was . 8.65 years for EA patients compared with 5.038 years (95% CI, 2.019 to 5.30; P = .003, log-rank) for AA patients. For p162 patients, the median OS was >.74 years (95% CI, 3.32 to 6.99) for EA patients and 1.85 years (95% CI, 0.978 to 4.50; P= .03, log-rank) for AA patients. Multivariate Cox regression analysis showed that race was an independent prognostic biomarker and the most impactful co-variate for OS (hazard ratio, 0.40; 95% CI, 0.00 to 0.69; P = .001). CONCLUSION Our work showed that AAs with p16+OPSCC have surprisingly poor clinical outcomes and are thus poor candidates for treatment de-escalation regimens. Caution should be exercised when extending clinical guidelines based on EA-majority studies to non-EA populations. [ABSTRACT FROM AUTHOR]

Published
2021
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57. WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer

Author

Kleer, Celina G, Zhang, Yanhong, Pan, Quintin, Gallagher, Gary, Wu, Mei, Wu, Zhi-Fen, and Merajver, Sofia D

Subjects
Inflammation, Vascular Endothelial Growth Factor A, rho GTP-Binding Proteins, vascular endothelial growth factor, Blotting, Western, Breast Neoplasms, CCN proteins, Transfection, DNA, Antisense, Cell Line, Neoplasm Proteins, CCN Intercellular Signaling Proteins, Insulin-Like Growth Factor Binding Proteins, motility, oncogene, rhoC GTP-Binding Protein, Cell Line, Tumor, Humans, RNA, Messenger, tumor suppressor gene, skin and connective tissue diseases, WNT-pathway, Cell Division, Research Article, Plasmids
Abstract

Background Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer. We found concordant and consistent alterations of two genes in 90% of IBC tumors when compared with stage-matched non-IBC tumors: overexpression of RhoC guanosine triphosphatase and loss of WNT-1 induced secreted protein 3 (WISP3). Further work revealed that RhoC is a transforming oncogene for human mammary epithelial (HME) cells. Despite the aggressiveness of the RhoC-driven phenotype, it does not quantitatively reach that of the true IBC tumors. We have demonstrated that WISP3 has tumor growth and angiogenesis inhibitory functions in IBC. We proposed that RhoC and WISP3 cooperate in the development of IBC. Methods Using an antisense approach, we blocked WISP3 expression in HME cells. Cellular proliferation and growth were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and anchorage-independent growth in a soft agar assay. Vascular endothelial growth factor (VEGF) was measured in conditioned medium by enzyme-linked immunosorbent assay. Results Antisense inhibition of WISP3 in HME cells increased RhoC mRNA levels and resulted in an increase in cellular proliferation, anchorage-independent growth and VEGF levels in the conditioned medium. Conversely, restoration of WISP3 expression in the highly malignant IBC cell line SUM149 was able to decrease the expression of RhoC protein. Conclusion WISP3 modulates RhoC expression in HME cells and in the IBC cell line SUM149. This provides further evidence that these two genes act in concert to give rise to the highly aggressive IBC phenotype. We propose a model of this interaction as a starting point for further investigations.

Published
2003

59. TriCurin, a novel formulation of curcumin, epicatechin gallate, and resveratrol, inhibits the tumorigenicity of human papillomavirus-positive head and neck squamous cell carcinoma

Author

Piao, Longzhu, primary, Mukherjee, Sumit, additional, Chang, Qing, additional, Xie, Xiujie, additional, Li, Hong, additional, Castellanos, Mario R., additional, Banerjee, Probal, additional, Iqbal, Hassan, additional, Ivancic, Ryan, additional, Wang, Xueqian, additional, Teknos, Theodoros N., additional, and Pan, Quintin, additional

Published
2016
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62. Elevated intrinsic cancer stem cell population in human papillomavirus-associated head and neck squamous cell carcinoma

Author

Zhang, Manchao, Kumar, Bhavna, Piao, Longzhu, Xie, Xiujie, Schmitt, Alessandra, Arradaza, Nicole, Cippola, Michael, Old, Matthew, Agrawal, Amit, Ozer, Enver, Schuller, David E., Teknos, Theodoros N., and Pan, Quintin

Subjects
Male, Human papillomavirus 16, Squamous Cell Carcinoma of Head and Neck, Papillomavirus Infections, Middle Aged, Immunohistochemistry, Article, Head and Neck Neoplasms, Risk Factors, Cell Line, Tumor, Carcinoma, Squamous Cell, Neoplastic Stem Cells, Humans, Female
Abstract

Human papillomavirus 16 (HPV16) is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), particularly the development of oropharyngeal squamous cell carcinoma (OPSCC). Cancer stem cells (CSCs) are resistant to conventional therapies, and it is postulated that they are responsible for disease recurrence and/or progression. Because the prognoses of patients with HPV16-positive and HPV-negative HNSCC are distinct, the authors sought to determine whether differences in the number of CSCs could account for this clinical observation.CSC populations in HPV16-positive and HPV-negative HNSCC were assessed using a proprietary assay based on expression of the enzyme aldehyde dehydrogenase (ALDH), an in vitro tumorsphere formation assay, and an in vivo limiting cell dilution in nonobese diabetic/severe combined immunodeficiency mice. A high-density tissue microarray was stained with ALDH1, a CSC marker, to determine the association between CSCs and HPV16-positive/HPV-negative OPSCC.HPV16-positive HNSCC had a greater intrinsic CSC pool than HPV-negative HNSCC. Inactivation of p53 has been identified as a major mechanism for the elevated CSC population in HPV16-positive HNSCC. In vivo limiting cell dilution experiments using tumors from patients with HPV16-positive and HPV-negative OPSCC indicated that the CSC frequency was 62.5-fold greater in an HPV16-positive OPSCC tumor than in an HPV-negative OPSCC tumor. Primary tumors from patients with HPV16-positive OPSCC were associated with elevated tumor ALDH1 staining, further extending the association between HPV16 and CSCs.The current data and the clinical observation that patients with HPV16-positive HNSCC respond more favorably to current treatment paradigms than patients with HPV-negative HNSCC support the suggestion that CSC phenotype is not homogeneous. Therefore, the reliance on the CSC number may be insufficient to accurately assess the potential of a particular tumor for disease recurrence and/or progression.

Published
2013

63. Surgical management of oropharyngeal squamous cell carcinoma: Survival and functional outcomes

Author

Kumar, Bhavna, primary, Cipolla, Michael J., additional, Old, Matthew O., additional, Brown, Nicole V., additional, Kang, Stephen Y., additional, Dziegielewski, Peter T., additional, Durmus, Kasim, additional, Ozer, Enver, additional, Agrawal, Amit, additional, Carrau, Ricardo L., additional, Schuller, David E., additional, Leon, Marino E., additional, Pan, Quintin, additional, Kumar, Pawan, additional, Wood, Valerie, additional, Burgers, Jessica, additional, Wakely, Paul E., additional, and Teknos, Theodoros N., additional

Published
2015
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65. WISP3 (CCN6) Is a Secreted Tumor-Suppressor Protein that Modulates IGF Signaling in Inflammatory Breast Cancer1

Author

Kleer, Celina G, Zhang, Yanhong, Pan, Quintin, and Merajver, Sofia D

Subjects
Inflammation, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, MAP Kinase Signaling System, Tumor Suppressor Proteins, Breast Neoplasms, Phosphoproteins, Neoplasm Proteins, Receptor, IGF Type 1, CCN Intercellular Signaling Proteins, Insulin-Like Growth Factor Binding Proteins, Culture Media, Conditioned, Biomarkers, Tumor, Insulin Receptor Substrate Proteins, Tumor Cells, Cultured, Humans, Insulin-Like Growth Factor I, Mitogen-Activated Protein Kinases, skin and connective tissue diseases, Research Article
Abstract

Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer. We have found that WISP3 is lost in 80% of human IBC tumors and that it has growth- and angiogenesis-inhibitory functions in breast cancer in vitro and in vivo. WISP3 is a cysteine-rich, putatively secreted protein that belongs to the CCN family. It contains a signal peptide at the N-terminus and four highly conserved motifs. Here, for the first time, we investigate the function of WISP3 protein in relationship to its structural features. We found that WISP3 is secreted into the conditioned media and into the lumens of normal breast ducts. Once secreted, WISP3 was able to decrease, directly or through induction of other molecule(s), the IGF-1-induced activation of the IGF-IR, and two of its main downstream signaling molecules, IRS1 and ERK-1/2, in SUM149 IBC cells. Furthermore, WISP3 containing conditioned media decreased the growth rate of SUM149 cells. This work sheds light into the mechanism of WISP3 function by demonstrating that it is secreted and that, once in the extracellular media, it induces a series of molecular events that leads to modulation of IGF-IR signaling pathways and cellular growth in IBC cells.

Published
2004

68. Elevated intrinsic cancer stem cell population in human papillomavirus-associated head and neck squamous cell carcinoma

Author

Zhang, Manchao, primary, Kumar, Bhavna, additional, Piao, Longzhu, additional, Xie, Xiujie, additional, Schmitt, Alessandra, additional, Arradaza, Nicole, additional, Cippola, Michael, additional, Old, Matthew, additional, Agrawal, Amit, additional, Ozer, Enver, additional, Schuller, David E., additional, Teknos, Theodoros N., additional, and Pan, Quintin, additional

Published
2013
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70. Genetic and Chemical Targeting of Epithelial-Restricted with Serine Box Reduces EGF Receptor and Potentiates the Efficacy of Afatinib

Author

Zhang, Manchao, primary, Taylor, Christopher E., additional, Piao, Longzhu, additional, Datta, Jharna, additional, Bruno, Paul A., additional, Bhave, Sanjay, additional, Su, Tizhi, additional, Lang, James C., additional, Xie, Xiujie, additional, Teknos, Theodoros N., additional, Mapp, Anna K., additional, and Pan, Quintin, additional

Published
2013
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71. Are Breast Tumor Stem Cells Responsible for Metastasis and Angiogenesis?

Author

MICHIGAN UNIV ANN ARBOR, Pan, Quintin, MICHIGAN UNIV ANN ARBOR, and Pan, Quintin

Abstract

Despite advances in the early detection and treatment of breast cancer, the mortality rate for 20% of patients with recurrences and/or metastases is nearly 100%. Thus, it is critical to understand the mechanism of breast cancer metastasis to allow for better therapies targeted at the cellular culprits of metastasis. The current dogma of metastasis is that most primary tumor cells have low metastatic potential, but rare cells, less than one in 10 million, within large primary tumors acquire metastatic capacity through somatic mutation. The metastatic phenotype includes the ability to disseminate from the primary tumor, survive in blood or lymphatic circulation, invade distant tissues, and establish macroscopic metastatic nodules. This dogma is primarily supported by animal models in which highly metastatic clones can develop from poorly metastatic cell lines if the process is facilitated by the isolation of metastatic nodules, expansion of the cells in vitro, and injection of these selected cells into recipient mice. However, no direct evidence of this genetic selection model has been documented in human tumors. A recent report demonstrated that a subpopulation of breast tumor cells (CD44+/CD24-(low)/Lineage-) isolated from breast cancer patient samples, even as few as 200 cells, were able to give rise to bulky tumors, greater than 1 cm in diameter, in NOD/SCID mice. Moreover, this discrete cell population has the ability to proliferate extensively, and to give rise to diverse and more differentiated cell types with reduced developmental or proliferative potential, suggesting that these highly tumorigenic CD44+/CD24-(low)/Lineage-cells may, indeed, be breast tumor stem cells. With this information, the authors propose an alternate model of metastasis and hypothesize that the breast tumor stem cells are the subpopulation of cells that are present in the heterogeneous primary breast tumor and possess the unique properties of an angiogenic and metastatic phenotype.

Published
2006

72. Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma

Author

Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Internal Medicine, Division of Pulmonary Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan ; Fax: (734) 936-9625 ; University of Michigan Medical Center, 1500 E. Medical Center Drive, 1904 Taubman Center, Ann Arbor, MI 48103, Marcus, Benjamin, Arenberg, Douglas A., Lee, Julia, Kleer, Celina G., Chepeha, Douglas B., Schmalbach, Cecelia E., Islam, Mozaffarul, Paul, Supriti, Pan, Quintin, Hanash, Samir, Kuick, Rork, Merajver, Sofia D., Teknos, Theodoros N., Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Internal Medicine, Division of Pulmonary Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan, Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan ; Fax: (734) 936-9625 ; University of Michigan Medical Center, 1500 E. Medical Center Drive, 1904 Taubman Center, Ann Arbor, MI 48103, Marcus, Benjamin, Arenberg, Douglas A., Lee, Julia, Kleer, Celina G., Chepeha, Douglas B., Schmalbach, Cecelia E., Islam, Mozaffarul, Paul, Supriti, Pan, Quintin, Hanash, Samir, Kuick, Rork, Merajver, Sofia D., and Teknos, Theodoros N.

Abstract

BACKGROUND The survival of patients with head and neck squamous cell carcinoma (HNSCC) remains unaffected despite recent therapeutic advances. To reverse this trend, reliable and clinically applicable markers of tumor aggressiveness must be identified. One such marker may be the tumor-associated macrophage content. The authors hypothesized that tumor-associated macrophages contribute to HNSCC aggressiveness, and the objective of the current study was to prove this hypothesis using mRNA expression analysis and a large cohort of clinical specimens. METHODS Oligonucleotide microarray analysis was performed on a prospective cohort of 20 patients with previously untreated oral cavity or oropharynx squamous cell carcinoma (OC/OP SCCA) and on normal oropharyngeal mucosa from 4 patients. After determining whether macrophage chemoattractants were produced by tumors, conditioned media from three HNSCC cell lines were used to quantify macrophage migration in an in vitro assay. A high-density tissue microarray of 102 patients with previously untreated OC/OP SCCA was stained immunohistochemically for CD68 to identify tissue macrophages, and the results were correlated with clinicopathologic data and survival. RESULTS Monocyte chemoattractant protein 1 was up-regulated significantly in tumors compared with normal mucosa (P = 0.0025; fold change = 1.89). All University of Michigan SCC tumor cell line conditioned media caused a significant increase in macrophage migration (P <0.05). Tissue microarray data revealed that macrophage content of the primary tumor was associated strongly with lymph node metastasis (P <0.0001), extracapsular lymph node spread (P = 0.0001), and advanced clinical disease stage (P = 0.0002). When it was evaluated along with other clinicopathologic data, the macrophage content was found to be an independent predictor of lymph node metastasis (P <0.0001). CONCLUSIONS Primary tumor macrophage content is a strong predictor of tumor aggressiveness in HNS

Published
2006

74. Suppression of NFkB by Tetrathiomolybdate Inhibits Tumor Angiogenesis and Enhances Apoptosis in Human Breast Cancer

Author

MICHIGAN UNIV ANN ARBOR, Pan, Quintin, MICHIGAN UNIV ANN ARBOR, and Pan, Quintin

Abstract

Angiogenesis, the formation of capillaries from pre-existing blood vessels, is essential for sustained growth of solid tumors. Numerous studies have shown that copper is required to modulate several pro-angiogenic factors. However, the specific effects of copper homeostasis on tumor angiogenesis have not been extensively studies. Our preliminary studies demonstrated that tetrathiomolybdate, a potent and novel copper chelator, blocks tumor growth and angiogenesis. We hypothesize that TM is inhibiting tumor angiogenesis by decreasing levels of VEGF, bFGF, IL-6, and IL-8 through interference with the NFkB signaling cascade. In this proposal, the molecular mechanism whereby TM regulates NFkB expression and activity will be investigated. We will establish if the NFkB transcription factor complexes, p50, p52, RelA, and RelB are regulated by TM using western blot analysis and gel shift assays. Furthermore, using a reporter gene system, we will ascertain if TM regulation of VEGF, bFGF, IL-6, and IL-S is a direct consequence of NFkB signal inhibition. The studies as outlined will help us better understand the role of copper deficiency in tumor angiogenesis and may lead to a more specific and potent global anti- angiogenic approach to treat breast cancer.

Published
2004

79. Suppression of KFkB by Tetrathiomolybdate Inhibits Tumor Angiogenesis and Enhances Apoptosis in Human Breast Cancers

Author

MICHIGAN UNIV ANN ARBOR, Pan, Quintin, MICHIGAN UNIV ANN ARBOR, and Pan, Quintin

Abstract

Angiogenesis, the formation of capillaries from pre-existing blood vessels, is essential for sustained growth of solid tumors. Numerous studies have shown that copper is required to modulate several pro-angiogenic factors. However, the specific effects of copper homeostasis on tumor angiogenesis have not been extensively studied. Our preliminary studies demonstrated that tetrathiomolybdate, a potent and novel copper chelator, blocks tumor growth and angiogenesis. We hypothesize that TM is inhibiting tumor angiogenesis by decreasing levels of VEGF, bFGF, IL-6, and IL-8 through interference with the NFkB signaling cascade. In this proposal, the molecular mechanism whereby TM regulates NFkB expression and activity will be investigated. We will establish if the NFkB transcription factor complexes, p50, p52, RelA, and RelB, are regulated by TM using Western blot analysis and gel shift assays. Furthermore, using a reporter gene system, we will ascertain if TM regulation of VEGF, bFGF, IL-6, and IL-8 is a direct consequence of NFkB signal inhibition. The studies as outlined will help us better understand the role of copper deficiency in tumor angiogenesis and may lead to a more specific and potent global anti-angiogenic approach to treat breast cancer.

Published
2003

90. Rap1GAP Promotes Invasion via Induction of Matrix Metalloproteinase 9 Secretion, Which Is Associated with Poor Survival in Low N-Stage Squamous Cell Carcinoma

Author

Mitra, Raj S., primary, Goto, Mitsuo, additional, Lee, Julia S., additional, Maldonado, Diana, additional, Taylor, Jeremy M.G., additional, Pan, Quintin, additional, Carey, Thomas E., additional, Bradford, Carol R., additional, Prince, Mark E., additional, Cordell, Kitrina G., additional, Kirkwood, Keith L., additional, and D'Silva, Nisha J., additional

Published
2008
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99. PKCε Phosphorylates and Mediates the Cell Membrane Localization of RhoA.

Author

Tizhi Su, Straight, Samuel, Liwei Bao, Xiujie Xie, Lehner, Caryn L., Cavey, Greg S., Teknos, Theodoros N., and Pan, Quintin

Subjects
CELL receptors, GENE mapping, ONCOGENES, PHOSPHOTRANSFERASES, RESEARCH funding, PRECIPITIN tests, CELL physiology
Abstract

Protein kinase Cε (PKCε) signals through RhoA to modulate cell invasion and motility. In this study, the multifaceted interaction between PKCε and RhoA was defined. Phosphopeptide mapping revealed that PKCε phosphorylates RhoA at T127 and S188. Recombinant PKCε bound to recombinant RhoA in the absence of ATP indicating that the association between PKCε and RhoA does not require an active ATP-docked PKCε conformation. Activation of PKCε resulted in a dramatic coordinated translocation of PKCε and RhoA from the cytoplasm to the cell membrane using time-lapse fluorescence microscopy. Stoichiometric FRET analysis revealed that the molecular interaction between PKCε and RhoA is a biphasic event, an initial peak at the cytoplasm and a gradual prolonged increase at the cell membrane for the entire time-course (12.5 minutes). These results suggest that the PKCε-RhoA complex is assembled in the cytoplasm and subsequently recruited to the cell membrane. Kinase inactive (K437R) PKCε is able to recruit RhoA to the cell membrane indicating that the association between PKCε and RhoA is proximal to the active catalytic site and perhaps independent of a PKCε-RhoA phosphorylation event. This work demonstrates, for the first time, that PKCε phosphorylates and modulates the cell membrane translocation of RhoA. [ABSTRACT FROM AUTHOR]

Published
2013
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100. Tetrathiomolybdate inhibits head and neckcancer metastasis by decreasing tumor cellmotility, invasiveness and by promoting tumorcell anoikis.

Author

Kumar, Pawan, Yadav, Arti, Patel, Samip N., Islam, Mozaffarul, Pan, Quintin, Merajver, Sofia D., and Teknos, Theodoros N.

Subjects
METASTASIS, TUMOR growth, CANCER cells, CANCER invasiveness, CYTOKINES
Abstract

Background: The metastatic spread of solid tumors is directly or indirectly responsible for most cancer-related deaths. Tumor metastasis is very complex and this process requires a tumor cell to acquire enhanced motility, invasiveness and anoikis resistance to successfully establish a tumor at a distal site. Metastatic potential of tumor cells is directly correlated with the expression levels of several angiogenic cytokines. Copper is a mandatory cofactor for the function of many of these angiogenic mediators as well as other proteins that play an important role in tumor cell motility and invasiveness. We have previously shown that tetrathiomolybdate (TM) is a potent chelator of copper and it mediates its anti-tumor effects by suppressing tumor angiogenesis. However, very little is known about the effect of TM on tumor cell function and tumor metastasis. In this study, we explored the mechanisms underlying TM-mediated inhibition of tumor metastasis. Results: We used two in vivo models to examine the effects of TM on tumor metastasis. Animals treated with TM showed a significant decrease in lung metastasis in both in vivo models as compared to the control group. In addition, tumor cells from the lungs of TM treated animals developed significantly smaller colonies and these colonies had significantly fewer tumor cells. TM treatment significantly decreased tumor cell motility and invasiveness by inhibiting lysyl oxidase (LOX) activity, FAK activation and MMP2 levels. Furthermore, TM treatment significantly enhanced tumor cell anoikis by activating p38 MAPK cell death pathway and by downregulating XIAP survival protein expression. Conclusions: Taken together, these results suggest that TM is a potent suppressor of head and neck tumor metastasis by modulating key regulators of tumor cell motility, invasiveness and anoikis resistance. [ABSTRACT FROM AUTHOR]

Published
2010
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