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

鉴定与癌症干细胞相互作用的生态位细胞并阐明其在乳腺癌中的功能

• 批准号: 21791255
• 负责人: SHIRAHANE Kengo
• 金额: $ 2.75万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791255/
• 关键词: 乳腺外科学; 乳癌; 間質細胞

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.

我们分析了在其他恶性肿瘤中作为癌症干细胞（CSC）标志物表达的几种标志物的群体比例，包括CD44、CD133、EpCAM、CXCR4和c-MET。结果发现，除EpCAM外，所有标记均有阳性和阴性群体。此外，我们量化了Notch配体的表达水平，据报道，Notch配体与csc的细胞分化和癌症间质相互作用有关。我们发现，乳腺癌细胞中单独表达的DLL1水平高于其他癌细胞。我们还量化了与宿主免疫应答相关的FAS/FasL和LCP1的表达水平。我们发现乳腺癌细胞中FAS/FasL水平较其他癌细胞低，表明乳腺癌细胞倾向于逃避宿主的免疫反应。由于有报道称LCP1高表达的病例与乳腺癌预后不良相关，因此LCP1可作为乳腺癌细胞抗肿瘤治疗耐药的新标志物。同时，我们从原代培养的结肠癌/胰腺癌等癌组织成纤维细胞中筛选了表达间充质/内皮干细胞（MSC/ESC）标记的亚群，并分析了它们的生物学功能。结果，我们发现CD10+癌症相关成纤维细胞显著增强侵袭性、转移和肿瘤形成。这些新的CSC/MSC特异性分子可能是乳腺癌有前景的诊断和治疗靶点。

项目成果

Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells.

• DOI: 10.1371/journal.pone.0012121
• 发表时间: 2010-08-12
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Cui L;Ohuchida K;Mizumoto K;Moriyama T;Onimaru M;Nakata K;Nabae T;Ueki T;Sato N;Tominaga Y;Tanaka M
• 通讯作者: Tanaka M

CD10+ Pancreatic Stellate Cells Enhance the Progression of Pancreatic Cancer

• DOI: 10.1053/j.gastro.2010.05.084
• 发表时间: 2010-09-01
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Ikenaga, Naoki;Ohuchida, Kenoki;Tanaka, Masao
• 通讯作者: Tanaka, Masao