» Articles » PMID: 15841211

Adipocyte-derived Collagen VI Affects Early Mammary Tumor Progression in Vivo, Demonstrating a Critical Interaction in the Tumor/stroma Microenvironment

Abstract

The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is well established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and beta-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIalpha3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI.

Citing Articles

Ovarian cancer-derived TGF-β1 induces cancer-associated adipocytes formation by activating SMAD3/TRIB3 pathway to establish pre-metastatic niche.

Gao T, Li J, Cheng T, Wang X, Wang M, Xu Z Cell Death Dis. 2024; 15(12):930.

PMID: 39719444 PMC: 11668853. DOI: 10.1038/s41419-024-07311-3.


Exploring the multifaceted role of obesity in breast cancer progression.

Kakkat S, Suman P, Turbat-Herrera E, Singh S, Chakroborty D, Sarkar C Front Cell Dev Biol. 2024; 12():1408844.

PMID: 39040042 PMC: 11260727. DOI: 10.3389/fcell.2024.1408844.


Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry.

Rujchanarong D, Spruill L, Sandusky G, Park Y, Mehta A, Drake R Glycobiology. 2024; 34(8).

PMID: 38869882 PMC: 11193881. DOI: 10.1093/glycob/cwae043.


Unveiling Collagen's Role in Breast Cancer: Insights into Expression Patterns, Functions and Clinical Implications.

Li X, Jin Y, Xue J Int J Gen Med. 2024; 17:1773-1787.

PMID: 38711825 PMC: 11073151. DOI: 10.2147/IJGM.S463649.


The coordinated activities of collagen VI and XII in maintenance of tissue structure, function and repair: evidence for a physical interaction.

Gregory C, Ma J, Lomeli S Front Mol Biosci. 2024; 11:1376091.

PMID: 38606288 PMC: 11007232. DOI: 10.3389/fmolb.2024.1376091.


References
1.
Thomasset N, Lochter A, Sympson C, Lund L, Williams D, Behrendtsen O . Expression of autoactivated stromelysin-1 in mammary glands of transgenic mice leads to a reactive stroma during early development. Am J Pathol. 1998; 153(2):457-67. PMC: 1852990. DOI: 10.1016/S0002-9440(10)65589-7. View

2.
Howell S, Doane K . Type VI collagen increases cell survival and prevents anti-beta 1 integrin-mediated apoptosis. Exp Cell Res. 1998; 241(1):230-41. DOI: 10.1006/excr.1998.4051. View

3.
Engelman J, Lisanti M, Scherer P . Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis. J Biol Chem. 1998; 273(48):32111-20. DOI: 10.1074/jbc.273.48.32111. View

4.
Sternlicht M, Lochter A, Sympson C, Huey B, Rougier J, Gray J . The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell. 1999; 98(2):137-46. PMC: 2853255. DOI: 10.1016/s0092-8674(00)81009-0. View

5.
Gladson C . The extracellular matrix of gliomas: modulation of cell function. J Neuropathol Exp Neurol. 1999; 58(10):1029-40. DOI: 10.1097/00005072-199910000-00001. View