title: Class A scavenger receptor deficiency exacerbates lung tumorigenesis by cultivating a procarcinogenic microenvironment in humans and mice.
abstract: BACKGROUND
  Genetic alterations on 8p22 have been implicated in multiple cancers, including lung cancer. In this region, genetic variants of the class A scavenger receptor (SR-A) gene have been associated with prostate cancer risk and have been highlighted as a potential susceptibility gene of cancer.
  
  
  OBJECTIVE
  To determine whether common polymorphisms in the SR-A gene are associated with human lung cancer risk and to clarify the role of SR-A in lung carcinogenesis.
  
  
  METHODS
  The relationship of three potentially functional polymorphisms (T-365C, T+25C, and Ala275Pro) in the SR-A gene with lung cancer risk was evaluated in 1287 lung cancer case subjects and 1261 control subjects from the Chinese population. At the same time, SR-A null mice were used to investigate its role in lung cancer development.
  
  
  RESULTS
  The T+25C polymorphism was independently associated with lung cancer risk and significantly correlated with decreased expression of SR-A. The decreased SR-A expression was also found in tumor tissues as compared with normal tissues. Depletion of SR-A boosted the growth and angiogenesis of implanted Lewis lung carcinoma in mice. The cancer-suppressing capability of SR-A was attributable to its expression in bone marrow-derived cells as evidenced by bone marrow transplantation. Further analysis revealed augmented expression of proangiogenic factors including matrix metalloproteinase-9 (MMP9) in SR-A-deficient mice, indicative of a more procarcinogenic microenvironment. Last, zoledronate, an MMP9 inhibitor, abrogated acceleration of tumor growth conferred by SR-A loss-of-function.
  
  
  CONCLUSIONS
  Evidence from the population study and mouse model strongly indicates that SR-A may function as a tumor modulator to inhibit lung cancer growth through affecting the tumor microenvironment.
authors.affiliation: Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ben
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bingqing
authors.initials: B
authors.lastname: Ma
authors.forename: Hui
authors.initials: H
authors.lastname: Bai
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.forename: Hanze
authors.initials: H
authors.lastname: Zhang
authors.forename: Qixing
authors.initials: Q
authors.lastname: Gong
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhou
authors.forename: Hanwen
authors.initials: H
authors.lastname: Zhang
authors.forename: Lingling
authors.initials: L
authors.lastname: Qian
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D044466:Asian People / Q000235:genetics; D018827:Carcinoma, Lewis Lung; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D011110:Polymorphism, Genetic; D051117:Scavenger Receptors, Class A / Q000172:deficiency* / Q000235:genetics*
chemical_list: D051117:Scavenger Receptors, Class A