Aquaporin‐1 gene deletion reduces breast tumor growth and lung metastasis in tumor‐producing MMTV‐PyVT mice

Abstract

Aquaporin 1 (AQP1) is a plasma membrane water-transporting protein expressed strongly in tumor microvascular endothelia. We previously reported impaired angiogenesis in implanted tumors in AQP1-deficient mice and reduced migration of AQP1-deficient endothelial cells in vitro. Here, we investigated the consequences of AQP1 deficiency in mice that spontaneously develop well-differentiated, luminal-type breast adenomas with lung metastases [mouse mammary tumor virus-driven polyoma virus middle T oncogene (MMTV-PyVT)]. AQP1(+/+) MMTV-PyVT mice developed large breast tumors with total tumor mass 3.5 ± 0.5 g and volume 265 ± 36 mm(3) (SE, 11 mice) at age 98 d. Tumor mass (1.6±0.2 g) and volume (131±15 mm(3), 12 mice) were greatly reduced in AQP1(-/-) MMTV-PyVT mice (P<0.005). CD31 immunofluorescence showed abnormal microvascular anatomy in tumors of AQP1(-/-) MMTV-PyVT mice, with reduced vessel density. HIF-1α expression was increased in tumors in AQP1(-/-) MMTV-PyVT mice. The number of lung metastases (5±1/mouse) was much lower than in AQP1(+/+) MMTV-PyVT mice (31±8/mouse, P<0.005). These results implicate AQP1 as an important determinant of tumor angiogenesis and, hence, as a potential drug target for adjuvant therapy of solid tumors.

Cardioprotective effect of valsartan in mice with short-term high-salt diet by regulating cardiac aquaporin 1 and angiogenic factor expression

“…The vessel density was reduced with abnormal microvascular structure in tumors, and the lung metastasis was greatly inhibited in AQP1 −/− MMTV-PyVT mouse model [32]. Meanwhile, the AQP1 mRNA and protein levels in mouse heart were significantly reduced by ischemia, hypoxia, and cardioplegia [25].…”

Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma

“…Moreover, it is confirmed that aquaporin 1 plays an active role in carcinogenesis, with an involvement in cell migration, proliferation, and angiogenesis [56][57][58][59]. Collectively, the facts mentioned above may account for much interest in identification of aquaporin 1 as a potential marker for MPM.…”

Expression of AQP1 Was Associated with Apoptosis and Survival of Patients in Gastric Adenocarcinoma

“…AQP1-expressing tumor cells have enhanced metastatic potential and increased local infiltration compared with those lacking AQP1 [6,19,20] . Knockdown of AQP1 in osteosarcoma cells can inhibit cell proliferation and significantly arrest cell cycle G1.…”

“…To date, studies have focused on the regulation of AQP1 expression in tumor cells and its role in pathogenesis, growth, metastatic potential and tumor progression [2,20] .…”