Adipocyte–Epithelial Interactions Regulate thein VitroDevelopment of Normal Mammary Epithelial Cells

Zangani, Danilo; Darcy, Kathleen M.; Shoemaker, Suzanne F.; Ip, Margot M.

doi:10.1006/excr.1998.4373

Cited by 61 publications

(52 citation statements)

References 66 publications

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“…28,29,31 For example, the adipokine leptin stimulates the proliferation of both normal and malignant breast epithelial cells by activation of leptin receptors on these cell types, leading to downstream activation of JAK/STAT and ERK/AP-1 pathways. 32 Adiponectin was shown to be protective against the development of postmenopausal breast cancer in two independent case-control studies.…”

Section: Adipocytes Mammary Development and Tumorigenesismentioning

confidence: 99%

Apoptosis Through Targeted Activation of Caspase8 (“ATTAC-mice”): Novel Mouse Models of Inducible and Reversible Tissue Ablation

Trujillo

Pajvani

Scherer³

2005

Cell Cycle

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Section: Adipocytes Mammary Development and Tumorigenesismentioning

confidence: 99%

Apoptosis Through Targeted Activation of Caspase8 (“ATTAC-mice”): Novel Mouse Models of Inducible and Reversible Tissue Ablation

Trujillo

Pajvani

Scherer³

2005

Cell Cycle

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“…Most primary breast tumors originate from ductal or intraductal epithelial cells. A number of groups have reported a strict dependence of breast cancer cell viability on surrounding stromal cell types in vivo (Johnston et al, 1992;Rahimi et al, 1994;Heber et al, 1996;Chamras et al, 1998;Rahimi et al, 1998;Zangani et al, 1999). Most of the studies focusing on cell-cell signaling mechanisms in the context of breast cancer have emphasized fibroblasts, myelofibroblasts, macrophages, and other inflammatory cells.…”

Section: Introductionmentioning

confidence: 99%

“…Many groups have shown that mammary ducts do not form properly without the appropriate interactions with adipose tissue and have identified various signaling mechanisms involved in this process (Howlett and Bissell, 1993;Zangani et al, 1999;Huss and Kratz, 2001). However, it is not known how adipocytes influence breast tumor cell behavior or whether any of the paracrine factors secreted by adipocytes cause changes in the phenotypic behavior of the malignant cells.…”

Section: Introductionmentioning

confidence: 99%

Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization

et al. 2003

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Mammary epithelial cells are embedded in a unique extracellular environment to which adipocytes and other stromal cells contribute. Mammary epithelial cells are critically dependent on this milieu for survival. However, it remains unknown which adipocyte-secreted factors are required for the survival of the mammary epithelia and what role these adipokines play in the process of ductal carcinoma tumorigenesis. Here, we take a systematic molecular approach to investigate the multiple ways adipocytes and adipokines can uniquely influence the characteristics and phenotypic behavior of malignant breast ductal epithelial cells. Microarray analysis and luciferase reporter assays indicate that adipokines specifically induce several transcriptional programs involved in promoting tumorigenesis, including increased cell proliferation (IGF2, FOS, JUN, cyclin D1), invasive potential (MMP1, ATF3), survival (A20, NFjB), and angiogenesis. One of the key changes in the transformed ductal epithelial cells associated with the cell cycle involves the induction of NFjB (five-fold) and cyclin D1 (three-fold). We show that by regulating the transcription of these molecules, the synergistic activity of adipocyte-derived factors can potentiate MCF-7 cell proliferation. Furthermore, compared to other stromal cell-secreted factors, the full complement of adipokines shows an unparalleled ability to promote increased cell motility, migration, and the capacity for angiogenesis. Adipocyte-secreted factors can affect tumorigenesis by increasing the stabilization of pro-oncogenic factors such as b-catenin and CDK6 as a result of a reduction in the gene expression of their inhibitors (i.e. p18). An in vivo coinjection system using 3T3-L1 adipocytes and SUM159PT cells effectively recapitulates the host-tumor interactions in primary tumors. Type VI collagen, a soluble extracellular matrix protein abundantly expressed in adipocytes, is further upregulated in adipocytes during tumorigenesis. It promotes GSK3b phosphorylation, b-catenin stabilization, and increased b-catenin activity in breast cancer cells and may critically contribute towards tumorigenesis when not counterbalanced by other factors.

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“…Mamalakis et al (2002) showed that relative to benign disease patients, the adipose tissue and prostatic tissue of CaP patients had reduced levels of AA and the o-3 lipid docosahexaenoic acid (DHA), and a reduced o-3 : o-6 PUFA ratio. Adipocyte/epithelial cell interactions have been shown to induce proliferation of prostate (Tokuda et al, 2003) and mammary (Rahimi et al, 1994) cancer cell lines and plays an important role in normal breast development (Zangani et al, 1999).…”

mentioning

confidence: 99%

Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs

et al. 2006

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Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 polyunsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations p5 mM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely. This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E 2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398. These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids.

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Adipocyte–Epithelial Interactions Regulate thein VitroDevelopment of Normal Mammary Epithelial Cells

Cited by 61 publications

References 66 publications

Apoptosis Through Targeted Activation of Caspase8 (“ATTAC-mice”): Novel Mouse Models of Inducible and Reversible Tissue Ablation

Apoptosis Through Targeted Activation of Caspase8 (“ATTAC-mice”): Novel Mouse Models of Inducible and Reversible Tissue Ablation

Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization

Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs

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