CAF from metastatic ovarian cancer (mCAF) vs CAF from non-metastatic ovarian cancer (nmCAF)
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ABSTRACT:
PROVIDER: PRJNA798275 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression profiling of CAF co-cultured with human oral squamous cell carcinoma (OSCC) cells compared with mono-cultured CAF. To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing co-cultured OSCC cells and CAF with monoculture controls. comparison 1: CAF co-cultured with OSCC vs. mono-cultured CAF comparison 2: OSCC co-cultured with CAF vs. mono-cultured OSCC 1.7X10(5) YD-10B OSCC cells and 1.7X10(5) CAF were seeded in the upper chamber and lower chamber, respectively, of 6-transwell plates containing collagen-coated 1 micrometer pore transmembrane filters (Becton Dickinson, Franklin Lakes, NJ, USA). Monoculture control samples were generated by culturing only CAF or OSCC on the same side of the filter as in the co-culture design.
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Project description:Gene expression profiling of CAF co-cultured with human oral squamous cell carcinoma (OSCC) cells compared with mono-cultured CAF. To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing co-cultured OSCC cells and CAF with monoculture controls.
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Project description:Cancer-associated fibroblasts (CAFs) have an important role in the tumor progression. CAFs are heterogeneous, and its subpopulation with distinct functions have been regarded as the major obstacle to CAF targeting therapy. However, it is still unclear how cancer cells mediate CAF subpopulations and create preferable tumor microenvironment for their metastasis. Because the CAF subpopulations are likely depending on the cancer cell subtypes and aggressiveness, it is conceivable the possibility that high-metastatic cancer cells have the capacity to induce the appropriate CAF subpopulation compared with low-metastatic cancer cells. To make it clear, by using the metastatic cancer cell line models of diffuse-type gastric cancer (DGC), we cultured the immortalized stomach fibroblasts with high-metastatic and low-metastatic DGC cell lines. And then, we compared the transcriptome profile of them by microarray analysis. It has shown that high-metastatic DGC cells can induce at least two types of CAF-like phenotypes: myofibroblastic feature and chemokine producing feature. We also found that these two features of fibroblasts were basically distributed in the different fibroblasts. These data indicated that high-metastatic DGC cells form the distinct CAF subpopulations.
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Project description:Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, we identified significantly higher levels of miR21 in exosomes and tissue lysate isolated from cancer associated adipocytes (CAA) and fibroblasts (CAF) compared to those from ovarian cancer cells. Functional studies and transcriptome analysis on miR21 transfected SKOV3 ovarian cancer cells revealed that miR21 could be transferred from CAA or CAF to ovarian cancer cells and modulate ovarian cancer apoptosis and chemoresistance through binding to its direct target APAF1. These data suggest that malignant phenotype of metastatic ovarian cancer cells can be modulated by miR21 delivered by exosomes derived from neighboring stromal cells in the omental tumor microenvironment.
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Project description:High-grade serous (HGS) ovarian cancer is the most common and aggressive ovarian cancer type, and the most lethal gynaecological disease 1,2. The major cause is its highly metastatic nature and the limited availability of effective therapies to oppose it. The omentum is a highly vascularised visceral depot of adipose tissue with immune functions, which becomes the preferential metastatic site in patients with HGS ovarian cancer 1,2. The omentum provides an environment that supports the rapid growth of metastatic tumours and their spread within the peritoneal cavity and adjacent organs 2,3. Research aimed at understanding the biology of metastatic tumours in the omentum is therefore essential to find strategies to oppose HGS ovarian cancer. To this aim, there is the need for in vitro models that faithfully recapitulate the microenvironment of HGS omental metastasis in patients.
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