title: 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.
authors: 11246 Health Sciences East Tower, University of California, San Francisco, CA 94143-0521, USA. alan.verkman@ucsf.edu.
authors: Cristina
authors: C
authors: Esteva-Font
authors: Byung-Ju
authors: BJ
authors: Jin
authors: A S
authors: AS
authors: Verkman
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics*; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D017353:Gene Deletion; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000556:secondary*; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics
chemical_list: D051398:Aquaporin 1
keywords: AQP1; endothelia; water channel