Editorial: Tumor Microenvironment and Cancer Cell Interactions in Solid Tumor Growth and Therapy Resistance

Abstract

Solid tumour tissues contain a tumour microenvironment (TME) which influences tumour progression and therapy resistance (Romano et al., 2021). TME is a network including noncancer stromal cells, extracellular matrix (ECM), growth factors, nutrients, blood and lymphatic vessels (Avagliano et al., 2020b), and its structure and components, depending on the type and location of the tumour, make each solid tumour unique (Granato et al., 2017;Avagliano et al., 2020a). Moreover, the TME plasticity leads to its evolution with disease and adaptation to cancer cell and environmental alterations. The components of TME by interacting with each other and with tumour cells generate a cancer niche that sustains immunosuppressive processes, drug resistance, cancer recurrence and dissemination that represent the main causes of cancer related deaths. This research topic includes eight articles, four reviews and four original articles (Figure 1). Some articles describe the role of extracellular matrix in tumour progression, metastasis formation and resistance to cancer therapy. Other articles describe both the effects of specific proteins in modulating growth, survival and invasion capability of cancer cells as well as the cross-talk between immune, stromal and tumour cells, mediated by cytokines, chemokines or metabolites, capable of creating immunosuppressive or immunostimulatory environments, in different tumour contexts.More specifically, Huang et al. exhaustively described in their review the interactions between tumour cells and extracellular matrix components, including both filamentous proteins (laminin, fibronectin, and collagen) and paracrine factors (cytokines, chemokines, growth factors, exosomes), involved together in the process of cell adhesion-mediated resistance (CAM-DR), essential in different tumours including multiple myeloma, non-Hodgkin's lymphoma, leukaemia and solid tumours. Finally, they focused on the therapeutic drugs and strategies that could reverse or inhibit CAM-DR process.Takahashi et al., in their review, after an introduction on the impact of fibroblasts in extracellular matrix remodelling, described the role of Meflin/Islr, a GPI-anchored cell surface protein, a novel marker of Mesenchymal Stromal/Stem Cells (MSC) and cancer associated

Exosome-mediated transfer of circRNA563 promoting hepatocellular carcinoma by targeting the microRNA148a-3p/metal-regulatory transcription factor-1 pathway

“…Recent studies have established a comprehensive role of TME in disease development, making it one of the most promising areas of oncological research[ 16 , 17 ]. Moreover, HCC cells can alter their surrounding microenvironment to promote their growth and metastasis[ 18 , 19 ].…”

Generation and Characterization of a Tumor Stromal Microenvironment and Analysis of Its Interplay with Breast Cancer Cells: An In Vitro Model to Study Breast Cancer-Associated Fibroblast Inactivation

“…The interactions between the TME and cancer cells dramatically influence the development and growth of solid tumors and the outcome of therapeutic strategies. Therefore, understanding if the TME is irreversibly differentiated into a pro-tumor phenotype or if some components of the TME can return to a less pro-tumorigenic or physiological phenotype is of great importance to both improve current anti-cancer therapies and to develop new therapeutic strategies [ 67 ].…”

A novel cuproptosis pattern and tumor immune microenvironment characterization in urothelial carcinoma of the bladder

“…For MIBC patients, radical cystectomy and lymphadenectomy may be operated according to the specific circumstances, combined with preoperative or postoperative radiotherapy, chemotherapy and neoadjuvant immunotherapy ( 6 ). Various researches have demonstrated the tumor microenvironment (TME) and genetic alterations occurring in cancer cells were directly associated with tumor progression and recurrence ( 7 ). Many patients have benefited from immune checkpoint inhibitors (ICI) targeting programmed cell death protein 1 (PD-1) and its ligand programmed cell death protein 1 (PD-L1), and these therapies are anticipated to prolong the survival time of MIBC patients ( 8 ).…”