Rlx-mediated stroma degradation in subcutaneous tumors mediates antitumor responses. (A,B) MMCs transduced with lentivirus vectors expressing mouse Rlx under Dox control (MMC-Rlx) or unmodified MMCs were used to establish tumors in neu-tg mice. Two days after transplantation, Dox was added to drinking water for selected groups of animals. Tumors were harvested 3 weeks after cell implantation, and tumor sections were analyzed for collagen IV (A) and laminin/CD45 (B). The scale bar represents 100 μm. Morphometry for collagen IV and quantification of CD45⁺ cells in tumor nests are shown on the right sides. Error bar represents SD. (C) Tumor size of MMC-Rlx tumors in neu-tg mice with Dox (○) and without Dox (■) treatment was measured over a period of 45 days. Each line represents one mice. (D) Kaplan-Meyer survival study in neu-tg mice (I.C. indicates immunocompetent) and CB17 SCID/beige (I.D. indicates immunodeficient) mice bearing MMC-Rlx tumors with and without Dox treatment (started at day 2 after tumor cell implantation.) Tumor size was measured daily. End point was the day when tumors reached a size of 1000 mm³  (n = 7 per group). (E) Tumor growth after injection of MMC-Rlx29 without Dox (■) and with Dox (○) treatment that was started at day 2 after tumor cell implantation. (F) Tumor growth after injection of MMC-Rlx29 without Dox (■) and with Dox (○) treatment that was started when tumors reached a size of approximately 70 mm.³