Tumorigenesis: cell defense against hypoxia?

Abstract

Microenvironmental elements can directly contribute to the induction and the maintenance of tumor. Oxygen is the main element in the cell microenvironment and hypoxia can affect the process of tumorigenesis. In response to hypoxia, cells change their pattern and characteristics. These changes suggest that it is not just adaptation, but some sort of cell defense against hypoxia. If hypoxia is corrected, then cell defense mechanisms are interrupted. An examination of the process of tumorigenesis helps to design better therapeutic strategies. A systematic review of the English literature was conducted by searching PubMed, Google Scholar, and ISI Web databases for studies on changes that defend and help cells to live in a hypoxic microenvironment. Cells respond to hypoxia by de-differentiation and an increase in heat shock proteins. Angiogenesis and deviation of inflammatory response in favor of hypoxic cell survival also defend and save the oxygen-starved cells from death. Finally, anti-angiogenic therapies and more hypoxia enhance metastasis, as tumors with low oxygen concentration are more malignant than tumors with high oxygen concentration. All these enable cells to migrate away from low oxygen areas and seek a more conducive microenvironment. Therapies that make the microenvironment more hypoxic need to be revised. This has been done for anti-angiogenic therapies, previously considered to be anti-tumor approaches. Effective therapies may be correcting therapies which direct the tumor microenvironment towards natural physical/chemical condition. Correcting therapies either bring back tumor cells to a normal form (correct tumor cells) or help the immune system to eradicate tumor cells which can not be corrected.

The role of the hypoxia‐Nrp‐1 axis in the activation of M2‐like tumor‐associated macrophages in the tumor microenvironment of cervical cancer

“…Macrophages are highly plastic cells that can infiltrate and be educated within the TME . Hypoxia represents a key micro‐environmental stressor that governs multiple phenomena associated with tumor progression, such as immune evasion, neoangiogenesis, and metastatic dissemination . As the hallmark feature of malignant tumors, hypoxia has been demonstrated to play a crucial role in TAM infiltration in the TME .…”

“…[8][9][10] Hypoxia represents a key microenvironmental stressor that governs multiple phenomena associated with tumor progression, such as immune evasion, neoangiogenesis, and metastatic dissemination. 11,12 As the hallmark feature of malignant tumors, hypoxia has been demonstrated to play a crucial role in TAM infiltration in the TME. [13][14][15] Notably, not only the number of TAMs but also their phenotype regulates carcinogenesis.…”

Expression of MMP-14 and prognosis in digestive system carcinoma: a meta-analysis and databases validation

“…Previous studies have shown MMP-14 was highly expressed in different tumor tissues, and its expression could promote the migration, invasion and metastasis of tumor cells in vitro and in vivo [71]. Potentially, MMP14 may play a crucial role in different biological processes of cancer and normal tissues [72].…”

Immunotherapy Using Oxygenated Water and Tumor‐Derived Exosomes Potentiates Antitumor Immune Response and Attenuates Malignancy Tendency in Mice Model of Breast Cancer

“…Supporters of oxygen therapy claim that low levels of oxygen enable tumor cells to adapt and thrive. Accordingly, oxygenation of tumor cells interferes with their proteomic and genomic changes and can destroy them [ 14 , 15 ]. The initial idea of oxygen therapy for cancer treatment using ozone or hydrogen peroxide, decomposing into oxygen, dates back decades ago [ 30 – 37 ].…”