Mammary adipose tissue and cancer cell growth: The role of adipose tissue in the tumor microenvironment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22009-e22009
Author(s):  
P. A. Carroll ◽  
L. Healy ◽  
J. Lysaght ◽  
M. Griffin ◽  
B. Dunne ◽  
...  

e22009 Background: Worldwide, the prevalence of obesity is rapidly increasing, correlating with a direct increase in cancer rates1. Adipose tissue is considered an important endocrine organ producing several important hormones and cytokines including leptin and adiponectin. Mechanisms for the role of obesity in cancer states includes the excess or unregulated secretion of adipocytokines from adipose tissue, and potentially the metabolic syndrome (a cluster of co-morbidities linked to metabolic dysregulation). Mammary adipose tissue is proposed to play a vital role in the microenvironment of normal and tumour states within the breast2. Breast adipose tissue is a good candidate to investigate effects of obesity and metabolic disturbances on cancer states. Methods: Peritumoural (PT) adipose tissue adjacent to the tumour and distal adipose tissue (D) within the breast was sampled in 10 patients. The tissue was processed and cultured for 72hrs in serum free minimal cytokine media. A-MB-231 and MCF-7 breast cancer cell lines were then cultured with this adipocyte conditioned media (ACM) and cell proliferation response was then measured using BrDU assays. The adipocytokine profile at the mRNA and protein level was measured in ACM and adipose tissue for comparative differences using RT-PCR, ELISA and Cytokine Profiler technology. Results: ACM from both sites promoted tumour cell survival. There was however, a differential cell proliferation response noted between the peritumoural (PT) ACM and that from the distant (D) ACM. Pro-inflammatory mediators (VEGF, TNF-α, EGF) were also demonstrated a trend to be differentially expressed between the 2 sites. Conclusions: Proliferation of breast cancer cell lines occurs in response to ACM, with differential effects seen between peritumoural ACM and distant ACM. This may be mediated through increased pro-inflammatory or pro- mitogenic adipocytokine production in adipose tissue surrounding tumour. Further analysis will determine what role obesity and the metabolic syndrome plays in the results noted. No significant financial relationships to disclose.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.


Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1196 ◽  
Author(s):  
Subhawat Subhawa ◽  
Teera Chewonarin ◽  
Ratana Banjerdpongchai

Houttuynia cordata Thunb. (HCT) and Piper ribesioides Wall. (PR) are common herbs that are widely distributed throughout East Asia and possess various biological properties including anti-cancer effects. However, in breast cancer, their mechanisms responsible for anti-carcinogenic effects have not been clarified yet. In this study, the inhibitory effects of HCT and PR ethanolic extracts on breast cancer cell proliferation, migration, invasion and apoptosis were examined. In MCF-7 and MDA-MB-231 cells, HCT and PR extracts at low concentrations can inhibit colony formation and induce G1 cell cycle arrest by downregulating cyclinD1 and CDK4 expression. Additionally, HCT and PR extracts also decreased the migration and invasion of both breast cancer cell lines through inhibition of MMP-2 and MMP-9 secretion. Moreover, the induction of apoptosis was observed in breast cancer cells treated with high concentrations of HCT and PR extracts. Not only stimulated caspases activity, but HCT and PR extracts also upregulated the expression of caspases and pro-apoptotic Bcl-2 family proteins in breast cancer cells. Altogether, these findings provide the rationale to further investigate the potential actions of HCT and PR extracts against breast cancer in vivo.


2014 ◽  
Vol 8 (2) ◽  
pp. 507-512 ◽  
Author(s):  
SUNG HOON KIM ◽  
HYE YOON LEE ◽  
SEUNG PIL JUNG ◽  
SANGMIN KIM ◽  
JEONG EON LEE ◽  
...  

2002 ◽  
Vol 172 (1) ◽  
pp. 187-198 ◽  
Author(s):  
F Pouliot ◽  
C Labrie

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta family of cytokines. The recent observation that BMPs can inhibit breast cancer cell proliferation in vitro suggests that BMPs or the BMP pathway may hold promise as therapeutic targets for the control of breast tumor growth in women. Better to understand the mechanism of BMP-induced growth arrest we examined the effect of BMP-2 and mediators of BMP-2 action on cell proliferation and p21(Cip1) expression in breast cancer cell lines. We show here that BMP-2 potently inhibited the proliferation of breast cancer cell lines that express both Smad1 and Smad4 (CAMA-1, MCF7, MDA-MB-231, T-47D, ZR-75-1), but not that of cells that only express Smad1 (MDA-MB-468). Growth inhibition correlated with up-regulation of p21 mRNA and protein levels. Up-regulation of p21 was resistant to cycloheximide but not to actinomycin D, suggesting that it occurred at the transcriptional level. Using p21 promoter-luciferase reporter constructs we mapped the BMP-responsive region of the p21 promoter to within 211 base pairs of the transcription start site. Induction of p21 promoter activity was rapid and coincided with up-regulation of p21 mRNA and protein levels. p21 promoter activity required both Smad1 and Smad4 and was induced by either BMP-2 or constitutively active type I BMP receptors. Moreover, the C-terminal SSVS region of Smad1 was necessary for activation of the p21 promoter by BMP-2. Taken together, these results indicate that the mechanism of BMP-induced p21 promoter activation involves BMP receptors and BMP Smads.


2009 ◽  
Vol 20 (10) ◽  
pp. 918-925 ◽  
Author(s):  
Ivan Vannini ◽  
Wainer Zoli ◽  
Francesco Fabbri ◽  
Paola Ulivi ◽  
Anna Tesei ◽  
...  

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