Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment

Cancers

Lauren A. Todd¹  Mia Stanic²  Rosamaria Lappano³  Marcello Maggiolini³  Violena Pietrobon⁴  Francesco Marincola⁴  Qi Cai⁴ 

[1] Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada;Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada;Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy;Kite Pharma Inc., Santa Monica, CA 90404, USA;

关键词: growth factors;    hormones;    hypoxia-inducible factors;    hypoxia;    immune exclusion;    immunotherapies;   

DOI  :  10.3390/cancers14030539

来源: DOAJ

【 摘 要 】

Hormones and growth factors (GFs) are signaling molecules implicated in the regulation of a variety of cellular processes. They play important roles in both healthy and tumor cells, where they function by binding to specific receptors on target cells and activating downstream signaling cascades. The stages of tumor progression are influenced by hormones and GF signaling. Hypoxia, a hallmark of cancer progression, contributes to tumor plasticity and heterogeneity. Most solid tumors contain a hypoxic core due to rapid cellular proliferation that outgrows the blood supply. In these circumstances, hypoxia-inducible factors (HIFs) play a central role in the adaptation of tumor cells to their new environment, dramatically reshaping their transcriptional profile. HIF signaling is modulated by a variety of factors including hormones and GFs, which activate signaling pathways that enhance tumor growth and metastatic potential and impair responses to therapy. In this review, we summarize the role of hormones and GFs during cancer onset and progression with a particular focus on hypoxia and the interplay with HIF proteins. We also discuss how hypoxia influences the efficacy of cancer immunotherapy, considering that a hypoxic environment may act as a determinant of the immune-excluded phenotype and a major hindrance to the success of adoptive cell therapies.

【 授权许可】

Unknown