Title:Modulation of intracellular pH in human ovarian cancer.
Volume: 16
Issue: 1
Author(s): C. Sanhueza, J. Araos, L. Naranjo, R. Villalobos, F. Westermeier, C. Salomon, A.R. Beltrán, M.A. Ramírez, J. Gutiérrez, F. Pardo and A. Leiva and L. Sobrevia
Affiliation:
关键词:
卵巢癌，细胞内pH值，NHE1、阿米洛利，缺氧，缺氧诱导因子。
摘要: To sustain tumor growth, the cancer cells need to adapt to low levels of oxygen (i.e., hypoxia) in the
tumor tissue and to the tumor-associated acidic microenvironment. In this phenomenon, the activation of the
sodium/proton exchanger 1 (NHE1) at the plasma membrane and the hypoxia-inducible factor (HIF) are critical
for the control of the intracellular pH (pHi) and for hypoxia adaptation, respectively. Interestingly, both of these
mechanisms end in sustaining cancer cell proliferation. However, regulatory mechanisms of pHi in human
ovary tissue and in malignant ascites are unknown. Additionally, a potential role of NHE1 in the modulation of
H+ efflux in human ovarian cancer cells is unknown. In this review, we discussed the characteristics of tumor
microenvironment of primary human ovarian tumors and tumor ascites, in terms of pHi regulatory mechanisms
and oxygen level. The findings described in the literature suggest that NHE1 may likely play a role in pHi
regulation and cell proliferation in human ovarian cancer, potentially involving HIF2α activation. Since ovarian
cancer is the fifth cause of prevalence of women cancer in Chile and is usually of late diagnosis, i.e., when the
disease jeopardizes peritoneal cavity and other organs, resulting in reduced patient survival, new efforts are
required to improve patient–life span and for a better understanding of the pathophysiology of the disease. The
potential advantage of the use of amiloride and amiloride–derivatives for cancer treatment in terms of NHE1
expression and activity is also discussed as a therapeutic approach in human ovarian cancer.
