Physicochemical aspects of the tumour microenvironment as drivers of vasculogenic mimicry

Abstract

Tumour vascularisation is vital for cancer sustainment representing not only the main source of nutrients and oxygen supply but also an escape route for single or clustered cancer cells that, once detached from the primary mass, enter the blood circulation and disseminate to distant organs. Among the mechanisms identified to contribute to tumour vascularisation, vasculogenic mimicry (VM) is gaining increasing interest in the scientific community representing an intriguing target for cancer treatment. VM indeed associates with highly aggressive tumour phenotypes and strongly impairs patient outcomes. Differently from vessels of healthy tissues, tumour vasculature is extremely heterogeneous and tortuous, impeding efficient chemotherapy delivery, and at the meantime hyperpermeable and thus extremely accessible to metastasising cancer cells. Moreover, tumour vessel disorganisation creates a self-reinforcing vicious circle fuelling cancer malignancy and progression. Because of the inefficient oxygen delivery and metabolic waste removal from tumour vessels, many cells within the tumour mass indeed experience hypoxia and acidosis, now considered hallmarks of cancer. Being strong inducers of vascularisation, therapy resistance, inflammation and metastasis, hypoxia and acidosis create a permissive microenvironment for cancer progression and dissemination. Along with these considerations, we decided to focus our attention on the relationship between hypoxia/acidosis and VM. Indeed, besides tumour angiogenesis, VM is strongly influenced by both hypoxia and acidosis, which could potentiate each other and fuel this vicious circle. Thus, targeting hypoxia and acidosis may represent a potential target to treat VM to impair tumour perfusion and cancer cell sustainment.

Deciphering the sequential changes of monocytes/macrophages in the progression of IDD with longitudinal approach using single-cell transcriptome

“…Increasing studies have reported not only that blood cells are composed of endothelial cells but also that vascular-like structures could be generated by non-endothelial cells (18,72). Macrophages are reported to regulate blood vessels growth, the new blood vessels could serve as passage for macrophages into ECM, and the interactions between macrophages and NP cells are potentially proangiogenic in degenerative IVD (73)(74)(75)(76). Notably, Barnett et al have demonstrated the significant finding that macrophages could form vascular mimicry channels in tumors or other hypoxic environments the same as cancer stem cells did (77).…”

Extracellular Lactic Acidosis of the Tumor Microenvironment Drives Adipocyte-to-Myofibroblast Transition Fueling the Generation of Cancer-Associated Fibroblasts

“…Extracellular matrix and soluble factors produced by both tumor and host stromal cells are also important elements of the TME, as well as hypoxia and acidosis, which are able to alter and reprogram almost every cell and even non-cellular components of the TME in a pro-tumoral way [ 32 ]. Focusing on the biochemical aspects of the TME, to date, much evidence has been provided about the crucial role exerted by hypoxia and acidosis in tumor progression, which made increasingly evident the intense alliance between them and cancer cells, with the common goal of tumor advancement and disease progression [ 8 ].…”

“…Notably, extracellular acidosis has been demonstrated to reprogram both tumor and host stromal cellular components toward disease advancement, actively participating in every step of cancer dissemination [ 5 , 6 , 7 ]. Much evidence to date has revealed the effects of the acidic TME on cancer cells, which, once adapted to such environmental conditions, gain an extremely plastic phenotype endowed with an increased ability to invade the surrounding tissues, enter into and survive in the blood/lymphatic circulation (anoikis resistance), and evade immune surveillance systems, as well as resist chemotherapy, radiation therapy, immunotherapy, and molecularly targeted therapies, overall accounting for an increased metastatic potential [ 5 , 8 , 9 , 10 ].…”

The role of mesenchymal stem cell-derived exosomes in tumor progression

“…Optimal tumor growth requires the generation of a specific microenvironment that enables enhanced viability, proliferation, invasion, and migration of malignant cells (Andreucci et al, 2022). Mesenchymal stem cells (MSC) are adult, self-renewable, rapidly proliferating stem cells that modulate the tumor microenvironment.…”