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Review
. 2022 Apr 29;11(4):394-406.
doi: 10.1093/stcltm/szac002.

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?

Vincent G J Guillaume  1 , Tim Ruhl  1 , Anja M Boos  1 , Justus P Beier  1
Affiliations
Review

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?

Vincent G J Guillaume et al. Stem Cells Transl Med. .

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.

Keywords: adipose-derived stem or stromal cells; cytokines; exosomes; fat grafting; lipotransfer; secretome; tumor cells; tumor microenvironment.

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Figures

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The oncogenic risk of ASCs sparks controversy. Numerous studies suggest a pro-oncogenic effect of ASCs on cancer cells. Contrariwise, other studies report an inhibitory and anti-oncogenic effect of ASCs, and clinical studies did not find elevated incidences of breast cancer recurrences after lipotransplantation. The divergent effects could be partially owed to the different behavior of ASCs in in-vitro and in-vivo studies versus clinical application as well as different reactions to various cancer entities.
Figure 1.
Figure 1.
Overview of the possible transplantation procedures of ASCs and potential therapeutic applications; harvested adipose tissue can be directly transplanted, digested, and centrifuged to enrich the graft with ASCs (CAL) or ASCs can be isolated, cultured for expenditure, and then transplanted, potential therapeutic applications for direct fat grafting and CAL are, eg, skin disorders or breast reconstruction; ex-vivo expanded ASCs are used, eg, for bone and nerve regeneration and in the field of tissue engineering. Abbreviations: ASCs, adipose-derived stem or stromal cells; CAL, cell-assisted lipotransfer.
Figure 2.
Figure 2.
Potential pro-oncogenic mechanisms of ASCs are depicted in this figure. ASCs may induce epithelial-to-mesenchymal transition (EMT), stimulate cancer stem cell growth/tumor growth, transdifferentiate toward CAA/CAF, enhance neovascularization of the tumor, and are capable of migration, the so-called homing, to the tumor. Abbreviations: ASCs, adipose-derived stem or stromal cells; CAA, cancer-associated adipocytes; CAF, cancer-associated fibroblasts.
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