| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Research Abstract |
We analyzed the ratio of populations expressing several markers, including CD44, CD133, EpCAM, CXCR4 and c-MET, which reported as the cancer stem cell (CSC) markers in the other malignancies. As the result, we found the positive and negative populations in all markers except EpCAM. Additionally, we quantified the expression levels of Notch ligands, which reported to be associated with cellular differentiation of CSCs and cancer-stromal interactions. We found that breast cancer cells expressed higher levels of DLL1 alone than those in other cancer cells. We also quantified the expression levels of FAS/FasL and LCP1 which are reported to be associated with the host's immune responses. We found the lower levels of FAS/FasL in breast cancer cells compared with other cancer cells, indicating that breast cancer cells tend to avoid the host's immune responses. Because the cases with higher expression of LCP1 were reported to be associated with poor prognosis in breast cancer, LCP1 can be the novel marker of breast cancer cells resistant to anti-tumor therapies. Meanwhile, we sorted the subpopulations expressing mesenchymal/endothelial stem cell (MSC/ESC) markers from primary-cultured fibroblasts derived from cancer tissues including colonic/pancreatic cancers and analyzed their biological functions. As the result, we found that CD10+ cancer-associated fibroblasts markedly enhanced invasiveness, metastasis, and tumor formation. These novel CSC/MSC specific molecules may be the promising diagnostic and therapeutic targets in breast cancer.
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