Extracellular matrix in obesity – cancer interactions

Abstract

Obesity or overweight is a risk factor for several health disorders such as type 2 diabetes, hypertension, and certain cancers. Furthermore, obesity affects almost all body systems including the extracellular matrix (ECM) by generating a pro-inflammatory environment, which are associated with abnormal secretions of several cytokines or hormonal substances, for example, insulin-like growth factors (IGFs), leptin, and sex hormones. These chemical mediators most likely have a great impact on the ECM. Accumulating evidence suggests that both obesity and ECM can influence tumor growth and progression through a number of chemical mediators. Conversely, cells in the connective tissue, namely fibroblasts and macrophages, support and aggravate the inflammatory situation in obesity by releasing several cytokines or growth factors such as vascular endothelial growth factor, epidermal growth factor, and transforming growth factor-beta (TGF-β). A wide range of functions are performed by TGF-β in normal health and pathological conditions including tumorigenesis. Breast cancer in postmenopausal women is a classic example of obesity-related cancer wherein several of these conditions, for example, higher levels of pro-inflammatory cytokines, impairment in the regulation of estrogen and growth factors, and dysregulation of different ECM components may favor the neoplastic process. Aberrant expressions of ECM components such as matrix metalloproteinases or matricellular proteins in both obesity and cancer have been reported by many studies. Nonstructural matricellular proteins, viz., thrombospondins, secreted protein acidic and rich in cysteine (SPARC), and Cyr61-CTGF-Nov (CCN), which function as modulators of cell-ECM interactions, exhibit protean behavior in cancer. Precise understanding of ECM biology can provide potential therapeutic targets to combat obesity-related pathologies.

Adipose-specific Vdr deletion alters body fat and enhances mammary epithelial density

“…Mammary adipocytes have been particularly well studied, as obesity is a known risk factor for breast cancer (13, 14) and significant cross-talk occurs between the epithelial and adipose tissue compartments in the gland (15, 16). Studies have demonstrated that adipocytes drive morphogenesis ex vivo and are essential for development of the mammary epithelium in vivo (15, 16).…”

Analysis of different components in the peritumoral tissue microenvironment of colorectal cancer: A potential prospect in tumorigenesis

“…The current study also examined the expression levels of hyaluronidase-1 (Hyal-1), a major tumor-derived hyaluronidase ( 15 ). Dysregulation of different ECM components may favor the neoplastic process ( 16 ). Various cells, belonging to the ECM, are also important in tumor initiation and progression.…”

Multifaceted Breast Cancer: The Molecular Connection With Obesity

“…Pathological events involved in obesity aethiology, such as inflammation and ECM modulation, also represents key steps in cancer development and progression (Barreto et al, ), so the hypothesis of a crucial implication of MMPs in obesity‐related carcinogenesis has been largely underlined. In the past, MMPs were thought to have a role exclusively in invasion and metastasis processes, but recent studies demonstrated that they are also deeply involved in several steps of cancer formation and during the growth of tumor cells by releasing of cell membrane bound precursors of some growth factors, or the inhibition of apoptosis pathways.…”