Leptin (Obesity Protein) and Breast Cancer Metastasis

Weight and BC re trial questioning link between fats and BC commented on earlier

RB


http://www.stormingmedia.us/52/5247/A524704.html

Leptin (Obesity Protein) and Breast Cancer Metastasis
Authors: Eva Surmacz; THOMAS JEFFERSON UNIV PHILADELPHIA PA

Abstract: Obesity in the United States has reached the alarming rate of -60% and is considered a second, after smoking, major killer. The link between obesity and breast cancer development has been postulated but the molecular mechanisms involved are not clear (1). Leptin, a 16 kDa protein product of the OB (obesity) gene is a cytokine reported to be secreted mainly from adipocytes and has been shown to control body fat mass and food intake by providing information to the central nervous system (2). The abundance of leptin is greater in females than in males and is regulated by steroid hormones and growth factors, such as estradiol, insulin and insulin-like growth factor 1(3-7). The levels of these substances are elevated in individuals with upper body obesity. This type of obesity correlates with increased breast cancer risk in post- menopausal women (1). In addition to its role as a regulator of appetite and metabolism, leptin can be involved in other processes, such as hematopoiesis, reproduction, and immunity (2,7) Recently, it has been demonstrated that leptin can act as a mitogen, chemoattractant, and angiogenic factor in different cell models (8-12). New data documented that human breast cancer cell lines and breast tumors may express leptin and leptin receptor (Ob-R) (8,9,13) In addition, leptin has been show to induce DNA synthesis in MCF-7 and T47D breast cancer cell lines (8,9). We hypothesized that in obese women, locally elevated levels of estrogens and insulin might increase the synthesis of leptin in adipocytes and/or epithelial cells, in effect leading to increased proliferation and/or migration in primary breast tumor.

[al from Canada]

I'm not surprised because there was a study that showed that metformin, a popular anti-diabetes drug, is synergistic in tumor shrinkage.

Thank you for posting this,
Al

[Gina]

WATERTOWN, Mass., May 26 /PRNewswire/ -- An innovative research study at Boston Biomedical Research Institute targeting a key protein in the uncontrolled production of breast cancer cells has received the highly prestigious Susan G. Komen Breast Cancer Foundation award. This novel approach by Boston Biomedical's Dr. Ruben Rene Gonzalez focuses on leptin, a protein which has been shown to promote both the proliferation of cancer cells and the formation of new blood vessels necessary for cancer growth, a process known as angiogenesis.
Although primarily known for its roles in obesity and reproduction, the protein leptin has recently been linked to breast cancer. "Because of leptin's active role in recruiting blood vessels for tumor growth, we theorized that blocking leptin's biological activity could be a novel approach to treating breast cancer," said Dr. Gonzalez.

To test this theory, the scientists designed non-toxic inhibitors of leptin 'signalling' -- or communication -- which they called leptin peptide antagonists, or LPAs. In their experiments, they found that the LPAs were able to block leptin-induced proliferation, adhesion and invasion of mammary cancer cells grown in tissue culture, and also in experimental mice. "Our results showed that LPAs significantly reduced the number and size of mammary tumors in these mice, and also reduced the incidence of metastasis to the liver," said Dr. Gonzalez.

This study at Boston Biomedical represents the first time that a therapeutic agent targeting leptin signaling has been tested to treat breast cancer, and the promising results did not go unnoticed by the Susan G. Komen Breast Cancer Foundation, a well-known national funder based in Dallas, Texas that is dedicated to eradicating breast cancer by advancing research, education, screening and treatment. Dr. Gonzalez also presented his findings at the 2005 annual meeting of the American Association for Cancer Research held in Anaheim, California.

"We are delighted to have this very promising step forward in the fight against breast cancer recognized by such a notable funder of cancer research," said Boston Biomedical's Director, Dr. Charles Emerson. "We are confident that these studies will lead to potent new therapeutics against this devastating disease."


-- Additional Information about Boston Biomedical Research Institute --
Boston Biomedical Research Institute is a not-for-profit institution dedicated to the understanding, treatment and prevention of specific human diseases including cancer, Alzheimer's disease, muscular dystrophy, diabetes and conditions such as obesity and reproductive health problems. When appropriate, the Institute collaborates in clinical studies of patients to apply the results of basic research to the cure of disease.


--Gina

Interesting. Thanks for the post.

I am still reading up on it but leptin seems closely involved with the bodies fat control mechanism.

I had not seen it reported as having other functions.

The more I read the more complex it all is.

RB

Re above this may be of interest.


RB


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

1: Endocrinology. 2005 Aug;146(8):3334-42. Epub 2005 May 19. Related Articles, Links
Click here to read
Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2.

Lappas M, Permezel M, Rice GE.

Department of Obstetrics and Gynaecology, University of Melbourne and Mercy Perinatal Research Centre, Mercy Hospital for Women, East Melbourne, Victoria, Australia. mlappas@unimelb.edu.au

Beyond their effects on central metabolic functions, leptin, resistin, and adiponectin have profound effects on a number of other physiologic processes, including immune function and inflammation. Although leptin, resistin, and adiponectin are produced in human placenta and adipose tissue, their immunoregulatory actions in these tissues are not known. Therefore, the aim of this study was to determine the effect of leptin, resistin, and adiponectin on the release of proinflammatory mediators in human placenta and sc adipose tissue. Samples were obtained from normal pregnancies at the time of cesarean section. Tissue explants (n = 5) were incubated in the absence (basal control) or presence of a leptin (1, 10, and 100 ng/ml), resistin (1, 10, and 100 ng/ml), and adiponectin (0.1 and 0.5 microg/ml). After 6 h incubation, the medium was collected, and the release of IL-1beta, IL-6, TNFalpha, prostaglandin (PG)F2alpha and PGE2 was quantified by ELISA. There was no effect of resistin on proinflammatory cytokine or prostaglandin release; however, leptin at 100 ng/ml and adiponectin at 0.1 and/or 0.5 microg/ml significantly increased the release of IL-1beta, IL-6, TNFalpha, and PGE2 from human placenta and adipose tissue. Although both leptin and adiponectin significantly increased PGF2alpha release from human placenta, there was no effect of these hormones on PGF2alpha release from adipose tissue. Furthermore, this leptin- and adiponectin-induced proinflammatory response could be abrogated by treatment with the antiinflammatory ERK1/2 MAPK inhibitor U0126, the peroxisomal proliferator-activated receptor-gamma ligand troglitazone, and the nuclear factor-kappaB inhibitor BAY 11-7082. Collectively, these data indicate that leptin and adiponectin activate proinflammatory cytokine release and phospholipid metabolism in human placenta and adipose tissue, and antiinflammatory agents can abrogate leptin- and adiponectin-induced inflammation.

PMID: 15905315 [PubMed - indexed for MEDLINE]