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 2
Adipocytes from collagen VI^+/– and collagen VI^–/– mice are less potent stimulators of tumor growth. Collagen VI also has greater impact on early than on late tumor progression. (A) SUM159-PT cells (1 × 10⁵) were coinjected into 8-week-old nude mice with the same number of isolated primary mammary adipocytes from collagen VI^+/+, collagen VI^+/–, collagen VI^–/– mice, or 3T3-L1 adipocytes. Four weeks after injection, the sizes of the resulting foci were measured. n = 4 mice in each cohort. Results are shown as mean ± SEM. (B) MMTV-PyMT transgenic mice were sacrificed, and large, late tumor sections (from lesions larger than 1,500 mm³) and some small transformed mammary tissue for early tumor samples (lesions smaller than 300 mm³) were isolated. Tumor pieces were transplanted into partially cleared mammary glands of collagen VI^+/+ and collagen VI^–/– mice (n = 4). After 3 weeks, whole mounts were made. The tumor focus had a dense cellular make-up in the WT background, compared with reduced cellular density in the collagen VI–null host. Tumor areas were quantitated. Note that the absence of collagen VI protein does not affect the growth of late-stage tumor transplants. *P < 0.05. (C) Collagen VI induces proteins whose gene products are upregulated on the DNA microarrays. MCF-7 cells were treated for 6 hours with collagen VI or collagen I (each at 30 μg/ml) and extracts were generated for Western blots. EGR2, ATF4, IL-8, and GDI-3 as a loading control were measured. The levels of induction seen were similar to those seen by DNA microarrays.