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脂肪来源干细胞促进原发性乳腺癌生长和转移的作用在自体脂肪移植存在的情况下会降低。

Promotion of Primary Murine Breast Cancer Growth and Metastasis by Adipose-Derived Stem Cells Is Reduced in the Presence of Autologous Fat Graft.

机构信息

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.

出版信息

Plast Reconstr Surg. 2019 Jan;143(1):137-147. doi: 10.1097/PRS.0000000000005142.


DOI:10.1097/PRS.0000000000005142
PMID:30589787
Abstract

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.

摘要

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。

相似文献

[1]
Promotion of Primary Murine Breast Cancer Growth and Metastasis by Adipose-Derived Stem Cells Is Reduced in the Presence of Autologous Fat Graft.

Plast Reconstr Surg. 2019-1

[2]
The Fate of the Adipose-Derived Stromal Cells during Angiogenesis and Adipogenesis after Cell-Assisted Lipotransfer.

Plast Reconstr Surg. 2018-2

[3]
Oncologic Safety and Efficacy of Cell-Assisted Lipotransfer for Breast Reconstruction in a Murine Model of Residual Breast Cancer.

Aesthetic Plast Surg. 2023-2

[4]
Fat Graft Safety after Oncologic Surgery: Addressing the Contradiction between In Vitro and Clinical Studies.

Plast Reconstr Surg. 2018-12

[5]
Interaction of Adipose-Derived Stromal Cells with Breast Cancer Cell Lines.

Plast Reconstr Surg. 2019-8

[6]
Effect of N-Acetylcysteine on Adipose-Derived Stem Cell and Autologous Fat Graft Survival in a Mouse Model.

Plast Reconstr Surg. 2015-8

[7]
Synergistic Effect of Adipose-Derived Stem Cells and Fat Graft on Wrinkles in Aged Mice.

Plast Reconstr Surg. 2019-6

[8]
Bone marrow-derived, alternatively activated macrophages enhance solid tumor growth and lung metastasis of mammary carcinoma cells in a Balb/C mouse orthotopic model.

Breast Cancer Res. 2012-5-22

[9]
Oncologic Safety of Fat Grafting for Autologous Breast Reconstruction in an Animal Model of Residual Breast Cancer.

Plast Reconstr Surg. 2019-1

[10]
The Efficacy of Cell-Assisted Lipotransfer Versus Conventional Lipotransfer in Breast Augmentation: A Systematic Review and Meta-Analysis.

Aesthetic Plast Surg. 2021-8

引用本文的文献

[1]
Adipose-derived stem cells enhance the tumorigenic potential of pre-malignant breast epithelial cells through paracrine activation of PI3K-AKT pathway.

Breast Cancer. 2025-5

[2]
The evolving tumor-associated adipose tissue microenvironment in breast cancer: from cancer initiation to metastatic outgrowth.

Clin Transl Oncol. 2024-12-25

[3]
Effectiveness and Safety of Different Methods of Assisted Fat Grafting: A Network Meta-Analysis.

Aesthetic Plast Surg. 2024-7

[4]
Breast fat grafting and cancer: a systematic review of the science behind enhancements and concerns.

Transl Breast Cancer Res. 2024-4-29

[5]
Exosomes from Adipose-Tissue-Derived Stem Cells Induce Proapoptotic Gene Expression in Breast Tumor Cell Line.

Int J Mol Sci. 2024-2-12

[6]
Meta-Analysis of the Oncological Safety of Autologous Fat Grafting After Breast Cancer on Basic Science and Clinical Studies.

Aesthetic Plast Surg. 2023-8

[7]
The oncological safety of autologous fat grafting: a systematic review and meta-analysis.

BMC Cancer. 2022-4-11

[8]
Comparison of the Efficacy and Safety of Cell-Assisted Lipotransfer and Platelet-Rich Plasma Assisted Lipotransfer: What Should We Expect from a Systematic Review with Meta-Analysis?

Cell Transplant. 2021

[9]
Phenotypic and Cellular Characteristics of a Stromal Vascular Fraction/Extracellular Matrix Gel Prepared Using Mechanical Shear Force on Human Fat.

Front Bioeng Biotechnol. 2021-2-26

[10]
The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction.

Int J Mol Sci. 2020-12-1

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