Abstract
Metabolic interplay between the tumor microenvironment and cancer cells is a potential target for novel anti-cancer approaches. Among stromal components, adipocytes and adipose precursors have been shown to actively participate in tumor progression in several solid malignancies. In adrenocortical carcinoma (ACC), a rare endocrine neoplasia with a poor prognosis, cancer cells often infiltrate the fat mass surrounding the adrenal organ, enabling possible crosstalk with the adipose cells. Here, by using an in vitro co-culture system, we show that the interaction between adipose-derived stem cells (ASCs) and the adrenocortical cancer cell line H295R leads to metabolic and functional reprogramming of both cell types: cancer cells limit differentiation and increase proliferation of ASCs, which in turn support tumor growth and invasion. This effect associates with a shift from the paracrine cancer-promoting IGF2 axis towards an ASC-associated leptin axis, along with a shift in the SDF-1 axis towards CXCR7 expression in H295R cells. In conclusion, our findings suggest that adipose precursors, as pivotal components of the ACC microenvironment, promote cancer cell reprogramming and invasion, opening new perspectives for the development of more effective therapeutic approaches.
Highlights
A growing tumor mass can be considered as a dynamic “pseudo-organ” in which active molecular and metabolic interaction is established between cancer cells and different populations of stromal, vascular and immune cells, constituting the complex cell network of the tumor microenvironment (TME) that modulates and is reciprocally modulated by the cancer mass [1]
To elucidate the molecular mechanisms underlying the higher motility/migratory ability in H295R cells after co-culture, we investigated the modulation of the stromal cell-derived factor 1 observed in H295R cells after co-culture, we investigated the modulation of the stromal cell-derived (SDF-1 or CXCL12)/CXCR4/CXCR7 axis in the different culturing conditions
We demonstrated that H295R cells and the adipose precursors reciprocally emerging mechanisms involving mature adipocytes and lipid metabolism have been reported to play stimulated each other to proliferate
Summary
A growing tumor mass can be considered as a dynamic “pseudo-organ” in which active molecular and metabolic interaction is established between cancer cells and different populations of stromal, vascular and immune cells, constituting the complex cell network of the tumor microenvironment (TME) that modulates and is reciprocally modulated by the cancer mass [1]. Far from being mere passive bystanders, adipocytes can store and release energy in the form of fatty acids and secrete specific adipose regulatory factors, namely adipokines They mediate both local and systemic effects, with particular implications for tumor initiation and growth, as well as local invasion and metastasis [4]. Conversion towards cancer-associated adipocytes (CAA) has been described, characterized by de-lipidation/de-differentiation, free fatty acid release and immunomodulatory adipokine secretion, as well as a shift in the OXPHOS metabolism towards glycolysis, resulting in the so-called reverse-Warburg effect [10,11,13,14,15,16,17] This re-programming of adipose cells provides the cancer cells with the substrates to fuel β-oxidation and the oncometabolites necessary for growth and invasion. We investigated the effects of the interaction between primary human ASCs and the ACC cell line H295R in an in vitro indirect co-culture system
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
