Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth
Kristin M Nieman,Hilary A. Kenny,Carla Penicka,Andras Ladanyi,Rebecca Buell-Gutbrod,Marion Zillhardt,Iris L. Romero,Mark S. Carey,Gordon B. Mills,Gökhan S. Hotamisligil,S. Diane Yamada,Marcus E. Peter,Katja Gwin,Ernst Lengyel +13 more
TLDR
It is shown that primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells, and that adipokines including interleukin-8 (IL-8) mediate these activities, and adipocytes provide fatty acids for rapid tumor growth.Abstract:
Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is unclear why tumor cells preferentially home to and proliferate in the omentum, yet omental metastases typically represent the largest tumor in the abdominal cavities of women with ovarian cancer. We show here that primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells, and that adipokines including interleukin-8 (IL-8) mediate these activities. Adipocyte-ovarian cancer cell coculture led to the direct transfer of lipids from adipocytes to ovarian cancer cells and promoted in vitro and in vivo tumor growth. Furthermore, coculture induced lipolysis in adipocytes and β-oxidation in cancer cells, suggesting adipocytes act as an energy source for the cancer cells. A protein array identified upregulation of fatty acid-binding protein 4 (FABP4, also known as aP2) in omental metastases as compared to primary ovarian tumors, and FABP4 expression was detected in ovarian cancer cells at the adipocyte-tumor cell interface. FABP4 deficiency substantially impaired metastatic tumor growth in mice, indicating that FABP4 has a key role in ovarian cancer metastasis. These data indicate adipocytes provide fatty acids for rapid tumor growth, identifying lipid metabolism and transport as new targets for the treatment of cancers where adipocytes are a major component of the microenvironment.read more
Citations
More filters
Journal ArticleDOI
Microenvironmental regulation of tumor progression and metastasis.
TL;DR: The paradoxical roles of the tumor microenvironment during specific stages of cancer progression and metastasis are discussed, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
Journal ArticleDOI
The Emerging Hallmarks of Cancer Metabolism
TL;DR: This Perspective has organized known cancer-associated metabolic changes into six hallmarks: deregulated uptake of glucose and amino acids, use of opportunistic modes of nutrient acquisition, useof glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, increased demand for nitrogen, alterations in metabolite-driven gene regulation, and metabolic interactions with the microenvironment.
Journal ArticleDOI
Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Douglas Hanahan,Lisa M. Coussens +1 more
TL;DR: Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types, which presents interesting new targets for anticancer therapy.
Journal ArticleDOI
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
TL;DR: It is argued that altered metabolism has attained the status of a core hallmark of cancer.
Journal ArticleDOI
Fundamentals of cancer metabolism
TL;DR: A conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis will progressively support the development of new strategies to treat human cancer.
References
More filters
Journal ArticleDOI
Metabolism of isolated fat cells. i. effects of hormones on glucose metabolism and lipolysis.
The Metabolism of Isolated Fat Cells: I. Effects of Hormones on Glucose Metabolism and Lipolysis
TL;DR: This article marks the beginning of Rodbell's interest in cell receptors and related his discovery that fat cells could be isolated from other cells by treating them with preparations of collagenase, and also found that insulin could stimulate glucose uptake.
Journal ArticleDOI
The biology of cancer: metabolic reprogramming fuels cell growth and proliferation
TL;DR: This review examines the idea that several core fluxes, including aerobic glycolysis, de novo lipid biosynthesis, and glutamine-dependent anaplerosis, form a stereotyped platform supporting proliferation of diverse cell types and regulates regulation of these fluxes by cellular mediators of signal transduction and gene expression.
Journal ArticleDOI
Ovarian Cancer Development and Metastasis
TL;DR: The initial steps of metastasis are regulated by a controlled interaction of adhesion receptors and proteases, and late metastasis is characterized by the oncogene-driven fast growth of tumor nodules on mesothelium covered surfaces, causing ascites, bowel obstruction, and tumor cachexia.