Physicochemical aspects of the tumour microenvironment as drivers of vasculogenic mimicry

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.

Automated summary

Tumour vascularisation is crucial for cancer sustainment, with vasculogenic mimicry (VM) gaining increasing interest as a potential target for cancer treatment. Unlike healthy tissue vessels, tumour vasculature is heterogeneous and tortuous, hindering efficient chemotherapy delivery and facilitating cancer cell metastasis. The disorganisation of tumour vessels contributes to a self-reinforcing vicious circle, promoting cancer malignancy and progression. Hypoxia and acidosis within tumours, which are hallmark features of cancer, induce vascularisation and create a permissive microenvironment for cancer progression and dissemination. Targeting hypoxia and acidosis may represent a potential strategy to treat VM and impede tumour perfusion and cancer cell sustainment.