HGF/c-Met Signalling in the Tumor Microenvironment
Recently, it has become clearer that tumor plasticity increases the chance that cancer cells could acquire new mechanisms to escape immune surveillance, become resistant to conventional drugs, and spread to distant sites.
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HGF/c-Met Signalling in the Tumor Microenvironment Alberto Zambelli, Giuseppe Biamonti, and Angela Amato
Abstract
Recently, it has become clearer that tumor plasticity increases the chance that cancer cells could acquire new mechanisms to escape immune surveillance, become resistant to conventional drugs, and spread to distant sites. Effectively, tumor plasticity drives adaptive response of cancer cells to hypoxia and nutrient deprivation leading to stimulation of neoangionesis or tumor escape. Therefore, tumor plasticity is believed to be a great contributor in recurrence and metastatic dissemination of cancer cells. Importantly, it could be an Achilles’ heel of cancer if we could identify molecular mechanisms dictating this phenotype. The reactivation of stem-like signalling pathways is considered a great determinant of tumor plasticity; in addition, a key role has been also attributed to tumor microenvironment (TME). Indeed, it has been proved that cancer cells interact with different cells in the
surrounding extracellular matrix (ECM). Interestingly, well-established communication represents a potential allied in maintenance of a plastic phenotype in cancer cells supporting tumor growth and spread. An important signalling pathway mediating cancer cell-TME crosstalk is represented by the HGF/c-Met signalling. Here, we review the role of the HGF/c-Met signalling in tumor-stroma crosstalk focusing on novel findings underlying its role in tumor plasticity, immune escape, and development of adaptive mechanisms. Keywords
HGF/c-Met signalling · Tumor microenvironment (TME) · Cellular crosstalk · Tumor heterogeneity · Cancer cell plasticity · Cancer stem cells (CSCs) · Mesenchymal stem cells (MSCs) · Adipokines · Hepatokines · Immune escape · Metabolic stress · Drug resistance · Metastasis · Inflammation · Neo-angiogenesis
A. Zambelli Unit of Oncology, Ospedale Papa Giovanni XXIII, Bergamo, Italy G. Biamonti · A. Amato (*) Institute of Molecular Genetics (IGM); National Research Council (CNR), Pavia, Italy e-mail: [email protected] © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021 A. Birbrair (ed.), Tumor Microenvironment, Advances in Experimental Medicine and Biology 1270, https://doi.org/10.1007/978-3-030-47189-7_2
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2.1
Introduction
2.1.1 T umor Plasticity, Cancer Stem Cells, and Tumor Microenvironment (TME) Traditionally, tumors from the same anatomical site are considered as one tumor entity due to the identification of common markers and shared clinical features. However, genome-wide analysis enabled molecular profiling of cancer cells showing that tumors of the same origin site could be divided into different subgroups based on distinct patterns of gene expression as in breast cancer [1, 2] and colon cancer [3–5]. Stochastic genetic changes have long been considered a trigger for tumor heterogeneity [6]; however, they well explain intra- and intra-tumor heterogeneity but they hardly mirror the remarkable
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