title: Caloric restriction reduces growth of mammary tumors and metastases.
abstract: We investigated the effects of caloric restriction (CR) on growth of tumors and metastases in the 4T1 mammary tumor model and found that CR, compared with normal diet, reduced the growth of mammary tumors and metastases and the total number of metastases that originated both spontaneously from the primary tumor and also experimentally from i.v. injection of the tumor cells. CR also decreased proliferation and angiogenesis and increased apoptosis in tumors. CR reduced levels of insulin, leptin, insulin-like growth factor 1, insulin-like growth factor binding protein 3 and increased adiponectin in tumors. We also demonstrated that tumors from CR mice possessed lower levels of transforming growth factor-β, lower intratumor deposition of collagen IV and reduced invasiveness due to a decrease in tumor secretion of active matrix metalloproteinase 9. Our results suggest that CR-induced metabolic and signaling changes affect the stroma and the tumor cells resulting in a microenvironment that prevents proliferation of breast tumors and their metastases.
authors.affiliation: Department of Cell Biology & Molecular Medicine and the Cardiovascular Research Institute, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, NJ 07103, USA. delorems@umdnj.edu
authors.forename: Mariana S
authors.initials: MS
authors.lastname: De Lorenzo
authors.forename: Erdene
authors.initials: E
authors.lastname: Baljinnyam
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Vatner
authors.forename: Patricio
authors.initials: P
authors.lastname: Abarzúa
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Rabson
mesh_terms: D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D031204:Caloric Restriction; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D004435:Eating; D005260:Female; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000517:prevention & control*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D016212:Transforming Growth Factor beta; D003094:Collagen; D020778:Matrix Metalloproteinase 2