Secretome Analysis of Breast Cancer-associated Adipose Tissue to Identify Paracrine Regulators of Breast Cancer Growth

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 May 20

PMID 28525384

Citations 13

Authors

Lore Lapeire

An Hendrix

Evelyne Lecoutere

Mieke Van Bockstal

Jo Vandesompele

Dawn Maynard

Geert Braems

Rudy Van den Broecke

Catherine Muller

Marc Bracke

Veronique Cocquyt

Hannelore Denys

Olivier de Wever

Affiliations

Soon will be listed here.

Abstract

Adipose tissue secretes a plethora of adipokines as evidenced by characterization of subcutaneous and visceral adipose tissue secretomes. However, adipose tissue composition and secretion pattern is depot and disease dependent, influencing the adipose tissue secretome. We investigated the secretome of cancer-associated adipose tissue (CAAT) explants from breast cancer patients and explored its role in breast cancer proliferation. CAAT proteins were identified by LC-MS/MS and human protein antibody arrays and stimulated proliferation of three breast cancer cell lines. Kinomics and transcriptomics of MCF-7 breast cancer cells treated with the secretome of CAAT revealed activation of Akt-, ERK- and JNK-pathways and differential expression of activator protein 1 (AP-1) and cAMP responsive element-binding protein (CREB) target genes. The cyclin-dependent kinase (CDK)4/6-inhibitor palbociclib significantly abrogated CAAT-enhanced breast cancer cell proliferation. Our work characterizes the specific breast CAAT protein secretome and reveals its pro-proliferative potency in breast cancer.

Citing Articles

Increased levels of versican and insulin-like growth factor 1 in peritumoral mammary adipose tissue are related to aggressiveness in estrogen receptor-positive breast cancer.

Mirra P, Parascandolo A, Marino G, DAlterio F, Zinna L, Desiderio A Mol Med. 2024; 30(1):201.

PMID: 39501160 PMC: 11539550. DOI: 10.1186/s10020-024-00968-8.

High BMI Is Associated with Changes in Peritumor Breast Adipose Tissue That Increase the Invasive Activity of Triple-Negative Breast Cancer Cells.

Miracle C, McCallister C, Denning K, Russell R, Allen J, Lawrence L Int J Mol Sci. 2024; 25(19).

PMID: 39408921 PMC: 11476838. DOI: 10.3390/ijms251910592.

White adipocyte dysfunction and obesity-associated pathologies in humans.

Hagberg C, Spalding K Nat Rev Mol Cell Biol. 2023; 25(4):270-289.

PMID: 38086922 DOI: 10.1038/s41580-023-00680-1.

Mutual impact of adipocytes and colorectal cancer cells growing in co-culture conditions.

Olszanska J, Pietraszek-Gremplewicz K, Domagalski M, Nowak D Cell Commun Signal. 2023; 21(1):130.

PMID: 37316878 PMC: 10265888. DOI: 10.1186/s12964-023-01155-8.

Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling.

Casado M, Canelles S, Arilla-Ferreiro E, Frago L, Barrios V Int J Mol Sci. 2023; 24(8).

PMID: 37108229 PMC: 10138313. DOI: 10.3390/ijms24087065.

References

Burbelo P, Wellstein A, Pestell R . Altered Rho GTPase signaling pathways in breast cancer cells. Breast Cancer Res Treat. 2004; 84(1):43-8. DOI: 10.1023/B:BREA.0000018422.02237.f9. View

Gil A, Olza J, Gil-Campos M, Gomez-Llorente C, Aguilera C . Is adipose tissue metabolically different at different sites?. Int J Pediatr Obes. 2011; 6 Suppl 1:13-20. DOI: 10.3109/17477166.2011.604326. View

Zobel D, Andreasen C, Burgdorf K, Andersson E, Sandbaek A, Lauritzen T . Variation in the gene encoding Krüppel-like factor 7 influences body fat: studies of 14 818 Danes. Eur J Endocrinol. 2009; 160(4):603-9. DOI: 10.1530/EJE-08-0688. View

Arseneault R, Chien A, Newington J, Rappon T, Harris R, Cumming R . Attenuation of LDHA expression in cancer cells leads to redox-dependent alterations in cytoskeletal structure and cell migration. Cancer Lett. 2013; 338(2):255-66. DOI: 10.1016/j.canlet.2013.03.034. View

Knudsen E, Witkiewicz A . Defining the transcriptional and biological response to CDK4/6 inhibition in relation to ER+/HER2- breast cancer. Oncotarget. 2016; 7(43):69111-69123. PMC: 5342463. DOI: 10.18632/oncotarget.11588. View

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A . Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034. PMC: 126239. DOI: 10.1186/gb-2002-3-7-research0034. View

Thangavel C, Dean J, Ertel A, Knudsen K, Aldaz C, Witkiewicz A . Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer. 2011; 18(3):333-45. PMC: 3624623. DOI: 10.1530/ERC-10-0262. View

Nalabolu M, Palasamudram K, Jamil K . Adiponectin and leptin molecular actions and clinical significance in breast cancer. Int J Hematol Oncol Stem Cell Res. 2014; 8(1):31-40. PMC: 3913152. View

Shaulian E, Karin M . AP-1 as a regulator of cell life and death. Nat Cell Biol. 2002; 4(5):E131-6. DOI: 10.1038/ncb0502-e131. View

10.

Weinberg R . The retinoblastoma protein and cell cycle control. Cell. 1995; 81(3):323-30. DOI: 10.1016/0092-8674(95)90385-2. View

11.

Yang X, Wood P, Ansell C, Quiton D, Oh E, Du-Quiton J . The circadian clock gene Per1 suppresses cancer cell proliferation and tumor growth at specific times of day. Chronobiol Int. 2009; 26(7):1323-39. DOI: 10.3109/07420520903431301. View

12.

Li J, Ou Z, Yu S, Gu X, Yang C, Chen A . The chemokine receptor CCR4 promotes tumor growth and lung metastasis in breast cancer. Breast Cancer Res Treat. 2011; 131(3):837-48. DOI: 10.1007/s10549-011-1502-6. View

13.

Trayhurn P . Adipocyte biology. Obes Rev. 2007; 8 Suppl 1:41-4. DOI: 10.1111/j.1467-789X.2007.00316.x. View

14.

Nieman K, Romero I, Van Houten B, Lengyel E . Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta. 2013; 1831(10):1533-41. PMC: 3742583. DOI: 10.1016/j.bbalip.2013.02.010. View

15.

Peinado J, Pardo M, de la Rosa O, Malagon M . Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity. Proteomics. 2012; 12(4-5):607-20. DOI: 10.1002/pmic.201100355. View

16.

Chen C, Hardy D, Mendelson C . Progesterone receptor inhibits proliferation of human breast cancer cells via induction of MAPK phosphatase 1 (MKP-1/DUSP1). J Biol Chem. 2011; 286(50):43091-102. PMC: 3234857. DOI: 10.1074/jbc.M111.295865. View

17.

Martin-Padura I, Gregato G, Marighetti P, Mancuso P, Calleri A, Corsini C . The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression. Cancer Res. 2011; 72(1):325-34. DOI: 10.1158/0008-5472.CAN-11-1739. View

18.

Alvarez-Llamas G, Szalowska E, de Vries M, Weening D, Landman K, Hoek A . Characterization of the human visceral adipose tissue secretome. Mol Cell Proteomics. 2007; 6(4):589-600. DOI: 10.1074/mcp.M600265-MCP200. View

19.

Kheterpal I, Ku G, Coleman L, Yu G, Ptitsyn A, Floyd Z . Proteome of human subcutaneous adipose tissue stromal vascular fraction cells versus mature adipocytes based on DIGE. J Proteome Res. 2011; 10(4):1519-27. PMC: 3070065. DOI: 10.1021/pr100887r. View

20.

Ouhtit A, Gaur R, Abdraboh M, Ireland S, Rao P, Raj S . Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic pathways and induction of apoptosis in breast cancer cells by a phytochemical super-cocktail: genes that underpin its mode of action. J Cancer. 2013; 4(9):703-15. PMC: 3842439. DOI: 10.7150/jca.7235. View