Balance of adiponectin and leptin modulates breast cancer cell growth (original) (raw)

Cell Research volume 18, pages 1154–1156 (2008)Cite this article

There is lack of information concerning how the ratio of adiponectin to leptin in serum affects breast cancer (Brca) proliferation. It is possible that the link between obesity and increased risk for aggressive Brca is in part due to the milieu of cytokines synthesized and released by the adipose tissue 1. Adiponectin (also known as adipocyte complement-related protein of 30 kDa (Acrp30)) and leptin are two specific cytokines secreted by the adipose tissue. Acrp30 serum levels decrease with increasing fatness while leptin levels increase. Functionally, they appear to oppose each other's actions. Acrp30 can block proliferation of Brca cells 2. In vitro assays have shown that a number of different Brca cell lines express one or both of the Acrp30 receptors and show reduced growth and/or increased apoptosis in response to Acrp30 3. Leptin has been implicated as a growth-promoting factor for Brca 1. Animal studies also support a role for leptin in mammary tumor development as evidenced by the fact that mice deficient in leptin, Lep ob Lep ob 4, or with non-functioning leptin receptors, Lepr db Lepr db 5, did not develop transgene-induced mammary tumors. It is possible that the levels of adiponectin and leptin receptors, as well as the balance of serum adiponectin and leptin, are critical factors in mammary tumorigenesis.

Here we have moved a step beyond assessing individual adipokines by determining the effects of a changing ratio between Acrp30 and leptin on human Brca cells. The actions of gAcrp30 have received very little attention in relation to Brca growth. We found that gAcrp30 is capable of decreasing cell proliferation of the MDA-ERα7 cell line (Figure 1A). Furthermore, when gAcrp30 and leptin were combined at ratios that simulate the serum levels of non-obese individuals there was a reduction in Brca cell proliferation and the MDA-ERα7 cells were more sensitive as compared to ER-negative MDA-wt cells (Figure 1C). This illustrates that the ratio of gAcrp30 to leptin as well as the ERα status of the cells can be determinants in Brca growth. Nutritional interventions that affect mammary tumor development will now be undertaken to investigate specific links between Brca and the ratio of Acrp30/gAcrp30 to leptin in vivo.

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Acknowledgements

This work is supported by The Breast Cancer Research Foundation and The Hormel Foundation, USA.

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Authors and Affiliations

  1. Hormel Institute, University of Minnesota, Austin, 55912, MN, USA
    Michael E Grossmann, Amitabha Ray, Soner Dogan, Nancy K Mizuno & Margot P Cleary

Authors

  1. Michael E Grossmann
  2. Amitabha Ray
  3. Soner Dogan
  4. Nancy K Mizuno
  5. Margot P Cleary

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Correspondence toMargot P Cleary.

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Grossmann, M., Ray, A., Dogan, S. et al. Balance of adiponectin and leptin modulates breast cancer cell growth.Cell Res 18, 1154–1156 (2008). https://doi.org/10.1038/cr.2008.293

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