From the Department of Microbiology and Immunology, the Division of Plastic and Reconstructive Surgery, Department of Surgery, and the Department of Pediatrics, Dalhousie University; and the Beatrice Hunter Cancer Research Institute.
Plast Reconstr Surg. 2019 Jan;143(1):137-147. doi: 10.1097/PRS.0000000000005142.
BACKGROUND: Cell-assisted lipotransfer involves enrichment of autologous fat with supraphysiologic numbers of adipose-derived stem cells to improve graft take. Adipose-derived stem cells have been shown to promote cancer progression, raising concerns over the safety of adipose-derived stem cells and cell-assisted lipotransfer in postoncologic breast reconstruction. The authors compared the effect of adipose-derived stem cells alone, cell-assisted lipotransfer, and conventional fat grafting on breast cancer growth and metastasis. METHODS: Proliferation and migration of murine 4T1 breast cancer cells cultured in control medium or mouse adipose-derived stem cell- or fat graft-conditioned medium were assessed by flow cytometry and scratch assay, respectively. Transcription levels of arginase-1, transforming growth factor-β, and vascular endothelial growth factor were assessed in adipose-derived stem cells and fat graft by quantitative reverse transcription polymerase chain reaction. An orthotopic mouse tumor model was used to evaluate breast cancer progression and metastasis. 4T1 cells were injected into the mammary pad of female BALB/c mice. Six days later, tumors were injected with saline, adipose-derived stem cells, fat graft, or cell-assisted lipotransfer (n = 7 per group). Two weeks later, primary tumors were examined by immunohistochemistry and lung metastasis was quantified. RESULTS: Adipose-derived stem cell-conditioned medium increased cancer cell proliferation (p = 0.03); migration (p < 0.01); and transcription of arginase-1, transforming growth factor-β, and vascular endothelial growth factor compared to fat graft-conditioned or control medium (p < 0.02). Tumor-site injection with adipose-derived stem cells alone led to increased primary tumor growth and lung metastasis compared to control, fat graft, or cell-assisted lipotransfer groups (p < 0.05). Adipose-derived stem cell injection increased CD31 vascular density in tumors (p < 0.01). CONCLUSION: Adipose-derived stem cells alone, but not conventional fat graft or cell-assisted lipotransfer, promote breast cancer cell proliferation and invasiveness in vitro and in vivo.
背景:细胞辅助脂肪转移术通过用超生理数量的脂肪来源干细胞来富集自体脂肪,以提高移植物的成活率。脂肪来源干细胞已被证明能促进癌症的发展,这引发了人们对脂肪来源干细胞和细胞辅助脂肪转移术在肿瘤后乳房重建中的安全性的担忧。作者比较了脂肪来源干细胞单独应用、细胞辅助脂肪转移术和常规脂肪移植对乳腺癌生长和转移的影响。
方法:通过流式细胞术和划痕试验分别评估了在对照培养基或小鼠脂肪来源干细胞或脂肪移植条件培养基中培养的鼠 4T1 乳腺癌细胞的增殖和迁移。通过定量逆转录聚合酶链反应评估脂肪来源干细胞和脂肪移植中的精氨酸酶-1、转化生长因子-β 和血管内皮生长因子的转录水平。使用原位小鼠肿瘤模型评估乳腺癌的进展和转移。将 4T1 细胞注射到雌性 BALB/c 小鼠的乳腺垫中。6 天后,用生理盐水、脂肪来源干细胞、脂肪移植或细胞辅助脂肪转移术(每组 7 只)注射肿瘤。2 周后,通过免疫组织化学检查原发性肿瘤,并量化肺转移。
结果:与脂肪移植条件培养基或对照培养基相比,脂肪来源干细胞条件培养基可增加癌细胞的增殖(p = 0.03);迁移(p < 0.01);以及精氨酸酶-1、转化生长因子-β 和血管内皮生长因子的转录(p < 0.02)。与对照组、脂肪移植组或细胞辅助脂肪转移术组相比,单独注射脂肪来源干细胞可导致原发性肿瘤生长和肺转移增加(p < 0.05)。脂肪来源干细胞注射增加了肿瘤中的 CD31 血管密度(p < 0.01)。
结论:单独的脂肪来源干细胞而非常规的脂肪移植或细胞辅助脂肪转移术可促进乳腺癌细胞在体外和体内的增殖和侵袭。
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