Jekyll and Hyde: the role of the microenvironment on the progression of cancer

Abstract

It is now recognized that the host microenvironment undergoes extensive change during the evolution and progression of cancer. This involves the generation of cancer-associated fibroblasts (CAFs), which, through release of growth factors and cytokines, lead to enhanced angiogenesis, increased tumour growth and invasion. It has also been demonstrated that CAFs may modulate the cancer stem cell (CSC) phenotype, which has therapeutic implications. The altered fibroblast phenotype also contributes to the development of an altered extracellular matrix (ECM), with synthesis of ECM isoforms rarely found in normal tissues, including tenascin-C isoforms and the fibronectin EDA isoform. There is also emerging evidence of how the tensile strength of the tumour-associated ECM may be modified and lead to altered signalling in tumour cells. The hypoxic environment of the tumour stimulates angiogenesis and also impacts on other aspects of cell signalling, including the c-met pathway and lysyl oxidasemediated signalling, which can directly promote tumour cell invasion. The inflammatory infiltrate associated with many solid tumours also modulates tumour function, having both anti-and pro-tumour effects. All of these components of the microenvironment provide potential targets for therapeutic attack, with a number of molecules already in clinical trials. It is also becoming evident that characterizing the tumour microenvironment can provide important prognostic and predictive information about tumours, independent of the tumour cell phenotype.

Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

“…Tumor growth depends on the interaction with tumor microenvironment consisting of non-leukocytic cells including endothelial cells and fibroblasts as well as leukocytes [26]. Tumor microenvironment is influenced by various inflammatory molecules.…”

Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours matter

“…The micro-environment provides signalling to mediate cell proliferation, differentiation and death, regulating tissue architecture and remodelling [70]. The micro-environment is also able to suppress and revert processes that ultimately lead to cancer.…”

“…It means that the micro-environment can disrupt tissue homeostasis and promote cancer development. The destabilization of tissue homeostasis has a variety of causes, including the production of toxic substances by the stromal cells and/or other cell types, ie leading to impairment of signalling molecules [70,71].…”

Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

“…A malignant tumor microenvironment (TME) or niche is an important factor in tumor growth, progression, metastasis, and drug resistance [1][2][3]. The genesis of TME is a dynamic, complex process that involves various intrinsic and extrinsic factors [1,2].…”

“…The genesis of TME is a dynamic, complex process that involves various intrinsic and extrinsic factors [1,2]. In the historical "seeds and soil" theory of tumorigenesis, tumor cells were regarded as "seeds" and stoma as "soil" [4], and a more-recent theory of TME has been developed [5].…”