Adipocyte is a non-trivial, dynamic partner of breast cancer cells

Abstract

While the participation of adipocytes is well known in tissue architecture, energy supply and endocrine processes, their implication during natural cancer history is just beginning to unfold. An extensive review of the literature concerning the impact of resident adipocytes on breast cancer development/progression was performed. This review provides in vitro and in vivo evidence that adipocytes located close to invasive cancer cells, referred to as cancer-associated adipocytes (CAAs), are essential for breast tumor development/progression. Their deleterious function is dependent, at least partly, on their crosstalk with invasive cancer cells. Indeed, this event leads to dramatic phenotypic and/or functional modifications of both cell types. Adipocytes exhibit delipidation and acquire a fibroblast-like shape. In parallel, cancer cell aggressiveness is exacerbated through increased migratory and invasive properties. Moreover, obesity is currently a sign of poor prognosis in human carcinomas. In this context, a high number of "obese" resident adipocytes might be predicted to be detrimental. Accordingly, there are some similarities between the molecular alterations observed in hypertrophied adipocytes and in CAAs. How adipocytes function to favor tumorigenesis at the molecular level remains largely unknown. Nevertheless, progress has been made recently and molecular clues are starting to emerge. Deciphering the cellular and molecular mechanisms behind the adipocyte-cancer cell heterotypic crosstalk is of great interest since it might provide new targets for improving diagnosis/prognosis and for the design of innovative therapeutic strategies. They might also improve our understanding of the relationship between obesity/metabolic disorders and cancer risk and/or poor patient outcome.

Gene expression differences in adipose tissue associated with breast tumorigenesis

“…Lipolysis of adjacent adipocytes by mammary epithelial cells occurs during lactation 29 ; this may be coopted by tumor epithelial cells to provide tumors with a source of energy. 30 The role of adipose tissue as not only fuel for tumor growth, but also in recruiting macrophages and stimulating an inflammatory response, may contribute to the less favorable outcomes of obese breast cancer patients. Levels of adipose tissue macrophages were 3-fold higher in adipose tissue from obese compared with lean individuals 31 and reductive mammoplasty specimens from obese women demonstrated increased number of macrophages and inflammatory response.…”

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development

“…12,13 Moreover, MMP-11 is expressed and secreted by adipocytes and has a negative regulatory function during adipogenesis. 4,6,14 Interestingly, in human tumors, invasive cancer cells induce MMP-11 expression by proximal adipocytes, which in turn leads to the accumulation of peritumor fibroblast-like cells, known to favor cancer cell survival and tumor progression. 6,14 However, how adipocyte-related MMP-11 acts at the physiological level remains largely unknown.…”

Desmoplasia: A Response or a Niche?

“…It is also consistent in the context of the premetastatic niche in which fi bronectin deposition has been shown to precede the homing of circulating tumor cells. The decrease in fat accumulation may be counterintuitive, however, considering the recent evidence that adipocytes can have protumorigenic activity and that obesity is a factor of poor prognosis in cancer ( 14 ). This aspect deserves further investigation.…”