Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment
J. Clin. Invest. Puneeth Iyengar, et al. 115:1163 doi:10.1172/JCI23424 [Go to this article.]

Figure 1
Lack of collagen VI leads to a reduction in tumor growth. (A) Whole-mount analysis of early hyperplasia in 6-week-old collagen VI^+/+ or collagen VI^–/– MMTV-PyMT transgenic mice. Bottom panel: whole mount from a WT mouse. (B) Collagen VI reduction in hyperplastic foci size. Quantitation of hyperplastic areas at 3 and 6 weeks. n = 5 mice per group. *P < 0.05 vs. WT. (C) Number of hyperplastic foci does not significantly depend on collagen VI presence or absence in the MMTV-PyMT mouse. Quantitation of the number of foci formed in the mammary glands of 3-week-old MMTV-PyMT mice. n = 5 mice per group. (D) A representative H&E stain of a mammary section taken from PyMT⁺ColVI^–/– and PyMT⁺ColVI^+/+ mice at 6 weeks of age. (E) Quantitation of tumor sizes of female and male PyMT⁺ mice at different ages. n = 10 for each group. The 3 largest lesions were measured in each mouse. (F) Adipocytes (adip), but not breast cancer cells, express collagen VI, whereas breast cancer cells, but not adipocytes, express the collagen VI receptor NG2/CSPG. RT-PCR was performed to determine expression levels of NG2 and collagen VI. Lane 1, human adipocytes; lane 2, Marker (Mr; DNA ladder); lanes 3 and 4, MCF-7 cells; lanes 5 and 6, MCF-7 cells with adipocyte-conditioned medium; lanes 7 and 8, 3T3-L1 adipocytes; lane 9, MCF-7 cells; lane 10, MCF-7 cells with adipocyte-conditioned medium. (G) Expression of collagen VI in mammary adipocytes and early- and late-stage tumors. Quantitative real-time PCR was conducted. GAPDH was used as an internal control. Values for early-stage tumor samples were arbitrarily set to 1.