Li Wenjie, Xu Haiqian, Qian Cheng
Department of Oncological Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Plastic and Aesthetic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Biomed Res Int. 2017;2017:7407168. doi: 10.1155/2017/7407168. Epub 2017 May 10.
Adipose tissue-derived mesenchymal stem cells (ASCs) improve the regenerative ability and retention of fat grafts for breast reconstruction in cancer patients following mastectomy. However, ASCs have also been shown to promote breast cancer cell growth and metastasis. For the safety of ASC application, we aimed to identify specific markers for the subpopulation of ASCs that enhance the growth of breast cancer.
ASCs and bone marrow-derived vascular endothelial progenitor cells (EPCs) were isolated from Balb/c mice. c-Kit-positive (c-Kit) or c-Kit-negative (c-Kit) ASCs were cocultured with 4T1 breast cancer cells. Orthotropic murine models of 4T1, EPCs + 4T1, and c-KitASCs + 4T1/EPCs were established in Balb/c mice.
In coculture, c-Kit ASCs enhanced the viability and proliferation of 4T1 cells and stimulated c-Kit expression and interleukin-3 (IL-3) release. In mouse models, c-KitASCs + 4T1/EPCs coinjection increased the tumor volume and vessel formation. Moreover, IL-3, stromal cell-derived factor-1, and vascular endothelial growth factor A in the c-KitASCs + 4T1/EPCs coinjection group were higher than those in the 4T1, EPCs + 4T1, and c-KitASCs + 4T1/EPCs groups.
c-Kit ASCs may promote breast cancer growth and angiogenesis by a synergistic effect of c-Kit and IL-3. Our findings suggest that c-Kit subpopulations of ASCs should be eliminated in fat grafts for breast reconstruction of cancer patients following mastectomy.
脂肪组织来源的间充质干细胞（ASC）可提高乳房切除术后癌症患者乳房重建中脂肪移植的再生能力和留存率。然而，ASC也已被证明可促进乳腺癌细胞的生长和转移。为了确保ASC应用的安全性，我们旨在鉴定ASC亚群中可促进乳腺癌生长的特异性标志物。
从Balb/c小鼠中分离出ASC和骨髓来源的血管内皮祖细胞（EPC）。将c-Kit阳性（c-Kit）或c-Kit阴性（c-Kit）的ASC与4T1乳腺癌细胞共培养。在Balb/c小鼠中建立4T1、EPC + 4T1以及c-Kit ASC + 4T1/EPC的原位小鼠模型。
在共培养中，c-Kit ASC增强了4T1细胞的活力和增殖，并刺激了c-Kit表达和白细胞介素-3（IL-3）释放。在小鼠模型中，c-Kit ASC + 4T1/EPC联合注射增加了肿瘤体积和血管形成。此外，c-Kit ASC + 4T1/EPC联合注射组中的IL-3、基质细胞衍生因子-1和血管内皮生长因子A高于4T1、EPC + 4T1以及c-Kit ASC + 4T1/EPC组。
c-Kit ASC可能通过c-Kit和IL-3的协同作用促进乳腺癌生长和血管生成。我们的研究结果表明，在乳房切除术后癌症患者乳房重建的脂肪移植中应去除ASC的c-Kit亚群。
