Identification of the niche cells interacting with cancer stem cells and elucidation of their functions in breast cancer

• Project/Area Number: 21791255
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Kyushu University
• Principal Investigator: SHIRAHANE Kengo Kyushu University, 大学病院, 助教 (10529803)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥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)
• Keywords: 乳腺外科学 / 乳癌 / 間質細胞

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.

Research Products

• [Journal Article] CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer. (2010)
  • Author(s): Ikenaga N, Ohuchida K, Mizumoto K, Cui L, Kayashima T, Morimatsu K, Moriyama T, Nakata K, Fujita H, Tanaka M.
  • Journal Title: Gastroenterology 139 Pages: 1041-1051
• [Journal Article] Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells. (2010)
  • Author(s): Cui L, Ohuchida K, Mizumoto K, Moriyama T, Onimaru M, Nakata K, Nabae T, Ueki T, Sato N, Tominaga Y, Tanaka M.
  • Journal Title: PLoS ONE 12 Pages: 12121-12121
• [Journal Article] CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer (2010)
  • Author(s): Ikenaga N, et al.
  • Journal Title: Gastroenterology Volume: 139 Pages: 1041-1051
  • Peer Reviewed
• [Journal Article] Prospectively isolated cancer-associated CD10+ fibroblasts have stronger interactions with CD133+ colon cancer cells than with CD133-cancer cells (2010)
  • Author(s): Lin Cui, et al.
  • Journal Title: PLoS ONE Volume: 5
  • Peer Reviewed
• [Journal Article] Tumor-stromal interactions with direct cell contacts enhance proliferation of human pancreatic carcinoma cells. (2009)
  • Author(s): Fujita H, Ohuchida K, Mizumoto K, Egami T, Miyoshi K, Moriyama T, Cui L, Yu J, Zhao M, Manabe T, Tanaka M.
  • Journal Title: Cancer Science 100 Pages: 2309-2317
• [Presentation] CD10 positive pancreatic stellate cells enhance the progression of pancreatic cancer. (2009)
  • Author(s): Ikenaga N, Ohuchida K, Mizumoto K, Tanaka M.
  • Organizer: 40th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Association,
  • Place of Presentation: Hawaii