1. Instigating, noninstigating, and responding human tumor specimens.
Instigating, noninstigating, and responding human tumor specimens. A, human luminal breast tumor (hBRCA-LBC) xenotransplantation model. Each of 4 surgical specimens (hBRCA-LBC 1 through 4) was implanted into 3 mice per cohort. Ctl, control. B, growth of responding tumors in environment (envt) established by hBRCA-LBC1 tumor specimens; n = 3 mice. Inset, Ki67 (brown) of responding tumor formed in the hBRCA-LBC1 environment; nuclei counterstained with hematoxylin (blue). C, responding tumors exposed to the noninstigating hBRCA-LBC2 or instigating hBRCA-LBC1 environments (top 2 rows); responding human LBC specimen (hBRCA-LBC 5) implanted into either instigating or control environments (bottom 2 rows). Tumors stained for p-STAT3 (red; column 1), VEGFR2 (red; column 2), CD24 (red; column 3), collagens (blue; column 4), and p-selectin (green; column 5); nuclei counterstained with DAPI (blue; columns 1, 2, 5), hematoxylin (blue; column 3), or Masson's Trichrome (red; column 4). Yellow arrows indicate blood vessels with exposed collagen; white arrows indicate blood vessels with intact endothelium. Scale bar, 100 μm for all images, except for p-selectin, where scale bar, 25 μm. D, microvessel density of responding tumors in indicated hBRCA-LBC tumor environments. Tumors were examined under ×40 magnification and 3 representative areas per tumor were analyzed; n = 3 tumors (9 images) for Matrigel, n = 3 tumors (9 images) for hBRCA-LBC1, n = 1 tumor (3 images) for hBRCA-LBC2, no tumors were recovered opposite hBRCA-LBC3 or hBRCA-LBC4. E, xenotransplantation model for responding human primary LBC (hBRCA-LBC5); n = 5 mice per group. F, growth kinetics of hBRCA-LBC5 implanted into either control Matrigel (black line) or LBC (red line) systemic environments. G, hBRCA-LBC5 vessel density in tumors recovered from indicated environments. Tumors were examined under ×40 magnification and 5 representative areas per tumor were analyzed. H, human cRCC xenotransplantation model. Each surgical specimen was implanted into 4 mice per cohort. I, growth kinetics of responding cRCC specimens in the Matrigel control or LBC systemic environments as measured by tumor volume at indicated time points. J, histopathologic features of human cRCC tissues recovered from mice bearing the LBC systemic environment (left) or in mice bearing Matrigel plugs (right). Top, hematoxylin and eosin (H&E) staining; bottom, immunohistochemical labeling of CD34+ endothelial cells (×200 magnification). Inset, tumor cells within grafts grown in LBC tumor-bearing mice express the human cRCC marker CAIX (×600 magnification). envt, environment. Also see Supplementary Figs. S5–S7.
Hanna S. Kuznetsov et al. Cancer Discovery 2012;2:
©2012 by American Association for Cancer Research