The Crosstalk Between Adipose-Derived Stem or Stromal Cells (ASC) and Cancer Cells and ASC-Mediated Effects on Cancer Formation and Progression—ASCs: Safety Hazard or Harmless Source of Tropism?

Abstract

Adipose-derived stem or stromal cells (ASCs) possess promising potential in the fields of tissue engineering and regenerative medicine due to their secretory activity, their multilineage differentiation potential, their easy harvest, and their rich yield compared to other stem cell sources. After the first identification of ASCs in humans in 2001, the knowledge of their cell biology and cell characteristics have advanced, and respective therapeutic options were determined. Nowadays, ASC-based therapies are on the verge of translation into clinical practice. However, conflicting evidence emerged in recent years about the safety profile of ASC applications as they may induce tumor progression and invasion. Numerous in-vitro and in-vivo studies demonstrate a potential pro-oncogenic effect of ASCs on various cancer entities. This raises questions about the safety profile of ASCs and their broad handling and administration. However, these findings spark controversy as in clinical studies ASC application did not elevate tumor incidence rates, and other experimental studies reported an inhibitory effect of ASCs on different cancer cell types. This comprehensive review aims at providing up-to-date information about ASCs and cancer cell interactions, and their potential carcinogenesis and tumor tropism. The extracellular signaling activity of ASCs, the interaction of ASCs with the tumor microenvironment, and 3 major organ systems (the breast, the skin, and genitourinary system) will be presented with regard to cancer formation and progression.

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

“…In addition, ASCs/MSCs are capable of modulating the metabolism of breast cancer cells by stimulating, for example, the upregulation of cluster of differentiation 36 (CD36), a fatty acid receptor, leading to an increased proliferation rate [ 113 ], or the upregulation of S100 calcium-binding protein A7, involved in cell cycle regulation [ 114 ]. Moreover, numerous studies demonstrate that cancer cells are able to educate ASCs/MSCs, resulting in an altered gene and protein expression [ 143 ]. The interaction with cancer cells increased the release of tumor-promoting cytokines such as CCLs, CXCLs, SDF, and EGF [ 105 , 117 ]; angiogenesis factors including VEGF, angiopoietins, EGF, galectin-1, IGF1, and keratinocyte growth factor (KGF) [ 102 , 115 , 118 , 144 ]; and EMT inducers such as TGFβ, platelet-derived growth factor D (PDGF-D), and stem cell factor (SCF) [ 106 , 118 , 145 ].…”

“…Recently, increasing evidence highlights that ASCs/MSCs are educated and de-differentiated by cancer cells and the TME, fueling malignancy and therapy resistance [ 226 , 227 ]. Cancer-cell-secreted factors and direct cancer cell–ASC/MSC contacts induce a pro-tumorigenic population of ASCs/MSCs, named cancer-associated MSCs (CA-MSCs) [ 143 ]. CA-MSCs have the ability to differentiate into multiple cell lineages, such as fibroblasts and adipocytes, suggesting that MSCs may play a key role in the generation of most stromal components of the TME.…”

Influence of Tamoxifen on Different Biological Pathways in Tumorigenesis and Transformation in Adipose-Derived Stem Cells, Mammary Cells and Mammary Carcinoma Cell Lines—An In Vitro Study

“…Thus, the data to date regarding the influence of tamoxifen on ASC are limited and partly very controversial. In particular, conflicting data regarding the role of ASC in cancer progression were reported, showing that in in vivo and in vitro experiments, ASC favored tumor growth and increased extracellular matrix deposition and vascularization [ 49 ]. On the one hand, some studies investigated the effect of tamoxifen in vitro on ASC and demonstrated that tamoxifen concentrations above 2 µM had cytotoxic effects on ASC in terms of apoptosis induction and proliferation inhibition [ 41 ].…”

“…In addition to the effect of tamoxifen on ASC, the interaction between ASC and mammary carcinoma cells has also been extensively studied. Overall, conflicting evidence emerged during recent years about the safety profile of ASC applications as ASC may induce tumor progression and invasion [ 49 ]. In this respect, it is still unclear whether preadipocytes act differently from mature adipocytes [ 33 ].…”

“…In this respect, it is still unclear whether preadipocytes act differently from mature adipocytes [ 33 ]. Deriving from the secretory activity of ASC with the secretion of chemokines, growth factors and other various cytokines, pro and anti-oncogenic effects of ASC were postulated [ 49 , 51 ]. By secreting more than 474 proteins, ASC influence their local tissue environment as well as a possible tumor environment [ 51 ].…”