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Accumulating evidence suggests that mesenchymal stem cells (MSCs) are recruited to the tumor microenvironment; however, controversy exists regarding their role in solid tumors. In this study, we identified and confirmed the presence of carcinoma-associated MSCs (CA-MSCs) in the majority of human ovarian tumor samples that we analyzed. These CA-MSCs had a normal morphologic appearance, a normal karyotype, and were nontumorigenic. CA-MSCs were multipotent with capacity for differentiating into adipose, cartilage, and bone. When combined with tumor cells in vivo, CA-MSCs promoted tumor growth more effectively than did control MSCs. In vitro and in vivo studies suggested that CA-MSCs promoted tumor growth by increasing the number of cancer stem cells. Although CA-MSCs expressed traditional MSCs markers, they had an expression profile distinct from that of MSCs from healthy individuals, including increased expression of BMP2, BMP4, and BMP6. Importantly, BMP2 treatment in vitro mimicked the effects of CA-MSCs on cancer stem cells, while inhibiting BMP signaling in vitro and in vivo partly abrogated MSC-promoted tumor growth. Taken together, our data suggest that MSCs in the ovarian tumor microenvironment have an expression profile that promotes tumorigenesis and that BMP inhibition may be an effective therapeutic approach for ovarian cancer, Introduction There is strong evidence that mesenchymal stem cells (MSCs) are recruited to the tumor microenvironment. Based on this tropism of MSCs for the tumor microenvironment, numerous studies have suggested [...]

The gene encoding COMM domain-containing 1 (COMMD1) is a prototypical member of the COMMD gene family that has been shown to inhibit both NF-κB- and HIF-mediated gene expression. NF-κB and HIF are transcription factors that have been shown to play a role in promoting tumor growth, survival, and invasion. In this study, we demonstrate that COMMD1 expression is frequently suppressed in human cancer and that decreased COMMD1 expression correlates with a more invasive tumor phenotype. We found that direct repression of COMMD1 in human cell lines led to increased tumor invasion in a chick xenograft model, while increased COMMD1 expression in mouse melanoma cells led to decreased lung metastasis in a mouse model. Decreased COMMD1 expression also correlated with increased expression of genes known to promote cancer cell invasiveness, including direct targets of HIF. Mechanistically, our studies show that COMMD1 inhibits HIF-mediated gene expression by binding directly to the amino terminus of HIF-1α, preventing its dimerization with HIF-1β and subsequent DNA binding and transcriptional activation. Altogether, our findings demonstrate a role for COMMD1 in tumor invasion and provide a detailed mechanism of how this factor regulates the HIF pathway in cancer cells., Introduction COMM domain-containing 1 (COMMD1), the first COMMD family member to be identified, is a pleiotropic factor that participates in multiple processes, including copper metabolism, sodium excretion, inflammatory responses, and [...]

Context.--Nonuterine high-grade serous carcinomas (HGSCs) are believed to arise most often from precursors in the fallopian tube referred to as serous tubal intraepithelial carcinomas (STICs). A designation of tubal origin has been suggested for all cases of nonuterine HGSC if a STIC is identified. Objective.--To highlight that many different types of nongynecologic and gynecologic carcinomas, including HGSC, can metastasize to the tubal mucosa and mimic de novo STIC. Data Sources.--A mini-review of several recently published studies that collectively examine STIC-like lesions of the fallopian tube. Conclusions.--The fallopian tube mucosa can be a site of metastasis from carcinomas arising elsewhere, and pathologists should exercise caution in diagnosing STIC without first considering the possibility of metastasis. Routinely used immunohistochemical stains can often be used to determine if a STIC-like lesion is tubal or nongynecologic in origin. In the context of uterine and nonuterine HGSC, STIC may represent a metastasis rather than the site of origin, particularly when widespread disease is present. (Arch Pathol Lab Med. 2017; 141:1313-1315; doi: 10.5858/arpa.2017-0231-RA), Worldwide, ovarian carcinoma is the seventh most common cancer and the eighth most common cause of death from cancer in women. (1) High-grade serous carcinoma (HGSC) is the most common [...]

A two-dimensional liquid phase separation of proteins from whole cell lysates coupled on-line to an electrospray-ionization time-of-flight (ESI-TOF) mass spectrometer (MS) is used to map the protein content of ovarian surface epithelial cells (OSE) and an ovarian carcinoma-derived cell line (ES2). The two dimensions involve the use of liquid isoelectric focusing as the first phase and nonporous silica reversed-phase HPLC as the second phase of separation. Accurate molecular weight (MW) values are then obtained upon the basis of ESI-TOFMS so that an image of isolectric point (pI) versus MW analogous to 2-D gel electrophoresis is produced. The accurate MW together with the pI fraction and corresponding hydrophobicity (%B) are used to tag each protein so that protein expression can be compared in interlysate studies. Each protein is also identified on the basis of matrix-assisted laser desorption--ionization (MALDI) TOFMS peptide mapping and intact MW so that a standard map is produced against which other cell lines can be compared. Quantitative changes in protein expression are measured in these interlysate comparisons using internal standards in the on-line ESI-TOFMS process. In the ovarian epithelial cell lines under study, it is shown that in the three pI fractions chosen for detailed analysis, over 50 unique proteins can be detected per fraction, of which 40% can be identified from web-based databases. It is also shown that when using an accurate MW to compare proteins in the OSE versus ovarian cancer sample, there are proteins highly expressed in cancer cells but not in normal cells. In addition, many of the proteins in the cancer sample appear to be down-regulated, as compared to the normal cells. This two-dimensional (2-D) liquid/mass mapping method may provide a means of studying proteins in interlysate comparisons not readily available by other methods.

Research has been conducted on the beta- and gamma-catenin that are vertebrate homologs of Drosophila armadilo. The results indicate that gamma-catenin functions as an oncogene.

Isolation and determination of the expression pattern of the deleted in colorectal cancer (DCC) Xenopus homologue, XDCC-alpha, helps assess the developmental modulation of the DCC gene expression and its involvement in vertebrate development. XDCC-alpha expression exhibits dynamic variations during development and the brain tissues and neural tubes of the growing embryo exhibit maximum XDCC-alpha levels. Treatments that varied mature neural structure formation prevent DCC expression, indicating the developmental modulation and its neural activation-induced expression.

A study of the relationship between cell cycle regulatory tumor suppressor proteins pRB and p53 in the p53-mediated DNA damage response reveals that G1 cell cycle arrest occurs before pRB phosphorylation and shows an accumulation of hypophosphorylated pRB bound to human papilloma viruses (HPVs) 16 E7. HPV E6 and E7 oncoproteins weaken the cell cycle during HPV infection and help in the accumulation of genetic alterations during tumorigenesis.