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8. Cytoplasmic and/or nuclear accumulation of the β‐catenin protein is a frequent event in human osteosarcoma

Author

Haydon, Rex C, Deyrup, Andrea, Ishikawa, Akira, Heck, Robert, Jiang, Wei, Zhou, Lan, Feng, Tao, King, David, Cheng, Hongwei, Breyer, Benjamin, Peabody, Terrance, Simon, Michael A, Montag, Anthony G, and He, Tong‐Chuan

Subjects
Pediatric, Genetics, Pediatric Cancer, Cancer, Clinical Research, Rare Diseases, Pediatric Research Initiative, Aetiology, 2.1 Biological and endogenous factors, Adult, Bone Neoplasms, Cell Nucleus, Cytoplasm, Cytoskeletal Proteins, DNA Mutational Analysis, DNA, Neoplasm, Exons, Female, Humans, Immunoenzyme Techniques, Male, Mutation, Osteosarcoma, Survival Rate, Trans-Activators, Treatment Outcome, beta Catenin, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of beta-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of beta-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for beta-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the beta-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of beta-catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating beta-catenin signaling in osteosarcoma. In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, beta-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of beta-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

Published
2002

9. Cytoplasmic and/or nuclear accumulation of the beta-catenin protein is a frequent event in human osteosarcoma.

Author

Haydon, Rex C, Deyrup, Andrea, Ishikawa, Akira, Heck, Robert, Jiang, Wei, Zhou, Lan, Feng, Tao, King, David, Cheng, Hongwei, Breyer, Benjamin, Peabody, Terrance, Simon, Michael A, Montag, Anthony G, and He, Tong-Chuan

Subjects
Cell Nucleus, Cytoplasm, Humans, Osteosarcoma, Bone Neoplasms, Cytoskeletal Proteins, Trans-Activators, DNA, Neoplasm, Immunoenzyme Techniques, Treatment Outcome, Survival Rate, DNA Mutational Analysis, Mutation, Exons, Adult, Female, Male, beta Catenin, DNA, Neoplasm, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of beta-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of beta-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for beta-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the beta-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of beta-catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating beta-catenin signaling in osteosarcoma. In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, beta-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of beta-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

Published
2002

11. Supplementary Table Legends, Figures S1 - S6 from Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube

Author

Eckert, Mark A., primary, Pan, Shawn, primary, Hernandez, Kyle M., primary, Loth, Rachel M., primary, Andrade, Jorge, primary, Volchenboum, Samuel L., primary, Faber, Pieter, primary, Montag, Anthony, primary, Lastra, Ricardo, primary, Peter, Marcus E., primary, Yamada, S. Diane, primary, and Lengyel, Ernst, primary

Published
2023
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12. Supplementary Table S4 from Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube

Author

Eckert, Mark A., primary, Pan, Shawn, primary, Hernandez, Kyle M., primary, Loth, Rachel M., primary, Andrade, Jorge, primary, Volchenboum, Samuel L., primary, Faber, Pieter, primary, Montag, Anthony, primary, Lastra, Ricardo, primary, Peter, Marcus E., primary, Yamada, S. Diane, primary, and Lengyel, Ernst, primary

Published
2023
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13. Data from Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube

Author

Eckert, Mark A., primary, Pan, Shawn, primary, Hernandez, Kyle M., primary, Loth, Rachel M., primary, Andrade, Jorge, primary, Volchenboum, Samuel L., primary, Faber, Pieter, primary, Montag, Anthony, primary, Lastra, Ricardo, primary, Peter, Marcus E., primary, Yamada, S. Diane, primary, and Lengyel, Ernst, primary

Published
2023
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15. Supplementary Figures 1-4 from Loss of E-Cadherin Promotes Ovarian Cancer Metastasis via α5-Integrin, which Is a Therapeutic Target

Author

Sawada, Kenjiro, primary, Mitra, Anirban K., primary, Radjabi, A. Reza, primary, Bhaskar, Vinay, primary, Kistner, Emily O., primary, Tretiakova, Maria, primary, Jagadeeswaran, Sujatha, primary, Montag, Anthony, primary, Becker, Amy, primary, Kenny, Hilary A., primary, Peter, Marcus E., primary, Ramakrishnan, Vanitha, primary, Yamada, S. Diane, primary, and Lengyel, Ernst, primary

Published
2023
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18. Uterine Malignancies

Author

Fleming, Gini F., Montag, Anthony C., Mundt, Arno J., Yamada, S.D., Chang, Alfred E., editor, Hayes, Daniel F., editor, Pass, Harvey I., editor, Stone, Richard M., editor, Ganz, Patricia A., editor, Kinsella, Timothy J., editor, Schiller, Joan H., editor, and Strecher, Victor J., editor

Published
2006
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23. Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion

Author

Kenny, Hilary A., Chiang, Chun-Yi, White, Erin A., Schryver, Elizabeth M., Habis, Mohammed, Romero, Iris L., Ladanyi, Andras, Penicka, Carla V., George, Joshy, Matlin, Karl, Montag, Anthony, Wroblewski, Kristen, Yamada, S. Diane, Mazar, Andrew P., Bowtel, David, and Lengyel, Ernst

Subjects
Metastasis -- Development and progression -- Genetic aspects, Mesothelium -- Properties, Ovarian cancer -- Development and progression -- Genetic aspects, Fibronectins -- Properties, Health care industry
Abstract

Ovarian cancer (OvCa) metastasizes to organs in the abdominal cavity, such as the omentum, which are covered by a single layer of mesothelial cells. Mesothelial cells are generally thought to be 'bystanders' to the metastatic process and simply displaced by OvCa cells to access the submesothelial extracellular matrix. Here, using organotypic 3D cultures, we found that primary human mesothelial cells secrete fibronectin in the presence of OvCa cells. Moreover, we evaluated the tumor stroma of 108 human omental metastases and determined that fibronectin was consistently overexpressed in these patients. Blocking fibronectin production in primary mesothelial cells in vitro or in murine models, either genetically (fibronectin 1 floxed mouse model) or via siRNA, decreased adhesion, invasion, proliferation, and metastasis of OvCa cells. Using a coculture model, we determined that OvCa cells secrete TGF-β1, which in turn activates a TGF-β receptor/RAC1/ SMAD-dependent signaling pathway in the mesothelial cells that promotes a mesenchymal phenotype and transcriptional upregulation of fibronectin. Additionally, blocking [α.sub.5] or [β.sub.1] integrin function with antibodies reduced metastasis in an orthotopic preclinical model of OvCa metastasis. These findings indicate that cancer-associated mesothelial cells promote colonization during the initial steps of OvCa metastasis and suggest that mesothelial cells actively contribute to metastasis., Introduction The biology of serous high-grade ovarian cancer (OvCa) is different from that of most other solid tumors, since OvCa is predominantly confined within the abdominal and pleural cavities and [...]

Published
2014
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31. Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects

Author

Luo, Xiaoji, Chen, Jin, Song, Wen-Xin, Tang, Ni, Luo, Jinyong, Deng, Zhong-Liang, Sharff, Katie A, He, Gary, Bi, Yang, He, Bai-Cheng, Bennett, Erwin, Huang, Jiayi, Kang, Quan, Jiang, Wei, Su, Yuxi, Zhu, Gao-Hui, Yin, Hong, He, Yun, Wang, Yi, Souris, Jeffrey S, Chen, Liang, Zuo, Guo-Wei, Montag, Anthony G, Reid, Russell R, Haydon, Rex C, Luu, Hue H, and He, Tong-Chuan

Published
2008
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33. Effects of Slide Storage on Detection of Molecular Markers by IHC and FISH in Endometrial Cancer Tissues From a Clinical Trial: An NRG Oncology/GOG Pilot Study

Author

Grushko, Tatyana A., primary, Filiaci, Virginia L., additional, Montag, Anthony G., additional, Apushkin, Marsha, additional, Gomez, Maria J., additional, Monovich, Laura, additional, Ramirez, Nilsa C., additional, Schwab, Carlton, additional, Kesterson, Joshua P., additional, Seward, Shelly M., additional, Method, Michael W., additional, Olopade, Olufunmilayo I., additional, Fleming, Gini F., additional, and Birrer, Michael J., additional

Published
2021
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34. Protocol for the examination of specimens from patients with soft tissue tumors of intermediate malignant potential, malignant soft tissue tumors, and benign/locally aggressive and malignant bone tumors

Author

Rubin, Brian P., Fletcher, Christopher D.M., Inwards, Carrie, Montag, Anthony G., Peabody, Terrance, Qualman, Stephen J., Rosenberg, Andrew E., Weiss, Sharon, and Krausz, Thomas

Subjects
College of American Pathologists -- Research, Medical protocols -- Evaluation, Tumors -- Diagnosis, Diagnostic specimens -- Analysis
Published
2006

35. Social isolation and the inflammatory response: sex differences in the enduring effects of a prior stressor

Author

Hermes, Gretchen L., Rosenthal, Louis, Montag, Anthony, and McClintock, Martha K.

Subjects
Cytokines -- Research, Carrageenin -- Research, Biological sciences
Abstract

Numerous epidemiological studies have demonstrated an association between persistent social isolation and 'all-cause' morbidity and mortality. To date, no causal mechanism for these findings has been established. Whereas animal studies have often reported short-term effects of social isolation on biological systems, the long-term effects of this adverse psychological state have been understudied. This is the first animal study to examine the effects of long-term social isolation from weaning through young adulthood on an innate inflammatory response linked to numerous disease processes. Results presented here offer a plausible link between vulnerability to disease and social neglect. For socially isolated male and female Sprague-Dawley rats, a naturally gregarious species, formation of a granuloma in response to a subcutaneous injection of carrageenin (seaweed) was significantly delayed compared with the response of animals housed in single-sex groups of five. Significant sex differences, however, emerged when an acute prior stressor was superimposed on the experience of chronic social isolation. In this context, isolated females produced a more robust inflammatory response than isolated males. This sexual dimorphism at the nexus of chronic social isolation, acute stress, and inflammatory processes may account for the observation in humans that men with low levels of social integration are more vulnerable to disease and death than women. innate immunity; cytokine; chemokine; corticosterone

Published
2006

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