Adult adipose-derived stem cells and breast cancer: a controversial relationship

Abstract

Breast cancer is the most common cancer in women and autologous fat grafting is an important clinical application in treatment of post-surgical deformities. The simplicity of fat grafting procedures and the absence of subsequent visible scar prompted an increasing interest for this technique. The plasticity of adipose-derived stem cells (ASCs) obtained from stromal vascular fraction (SVF) of adult adipose tissue provided exciting perspectives for regenerative medicine and surgery. The recent discovery that SVF/ASC enrichment further ameliorates clinical efficacy of grafting ASCs suggest as ASC-mediated new adipogenesis and vasculogenesis. ASC adipogenic differentiation involves Akt activity and EGFRs, FGFRs, ERbB2 receptor-mediated pathways that also play a pivotal role in the regulation of breast cancer growth. Moreover, the finding that platelet-derived growth factors and hormones improved long-term maintenance of fat grafting raises new concerns for their use during breast reconstruction after cancer surgery. However, it remains unclear whether grafted or resident ASCs may increase the risk of de novo cancer development or recurrence. Preliminary follow-up studies seem to support the efficacy and safety of SVF/ASCs enrichment and the additional benefit from the combined use of autologous platelet-derived growth factors and hormones during breast reconstruction procedures. In the present review we highlighted the complex interplay between resident or grafted ASCs, mature adipocytes, dormant or active breast cancer cells and tumor microenvironment. Actually, data concerning the permissive role of ASCs on breast cancer progression are contrasting, although no clear evidence speaking against their use exists.

Adipose-Derived Stem Cells (ASC) Communicate with Residual Breast Cancer Cells

“…In summary, this means that ASC and breast cancer cells interact with each other in a complex dynamic manner and therefore influence the tumor behavior dramatically in a way that an increased risk in the post-oncological breast reconstruction by cell-assisted autologous lipotransfer could exist [4,10]. Previous findings indicate that the proximity and direct cell-cell interactions between ASC and breast cancer cells are a requirement to transmit signals for the induced cell growth [15].…”

“…A subcutaneous injection of a direct co-culture of ASC with breast cancer cells (MDA-MB-231) injected into a mouse exhibited a tumor ten times larger and an increased capacity of metastasis than an injection of a MDA-MB-231 isolate [17]. In this context, adipose-derived stem cells could communicate intercellularly with breast cancer cells by building gap junctions and substitute components with a low molecular weight among each other [10]. The presence of gap junctions correlates with a tightened invasive phenotype of both cell types [17].…”

“…Several studies indicate that adipose-derived stem cells enhance the angiogenesis, prohibit the apoptosis and support the differentiation of the adipocytes by secretion of growth factors, cytokines and chemokines [6,9,10]. The understanding that the enrichment of grafts with adipose-derived stem cells improves the clinical efficiency has led to the innovative use of ASC in post-oncological breast reconstruction.…”

“…The understanding that the enrichment of grafts with adipose-derived stem cells improves the clinical efficiency has led to the innovative use of ASC in post-oncological breast reconstruction. Thereby frequent complications that occur in the conventional fat transplantation, like necrosis, are avoided [10].…”

In Vitro Effects of Adipose-Derived Stem Cells on Breast Cancer Cells Harvested From the Same Patient

“…On the other hand, scientists opposed to clinical fat grafting argue that the clinical studies are limited by few prospective trials, short overall follow-up time frames, and small study populations. [10][11][12][13][14][15][16][17] Our aim in this study is to investigate the in vitro response of BrCa cells to ASCs from the same patient in a coculture model with regards to cell migration in a more clinically applicable model, specifically eliminating the use of banked resilient cancer cell lines and the use of adipose and BrCa specimens from different patients. We strive to answer the question: Is ASC enriched fat grafting to breast safe following oncologic surgery of the breast with potential remnant BrCa and is this procedure safe for augmentation in young woman with a strong family history of BrCa with potentially undetected or dormant cancer cells in the breast?…”