Abstract 5239: Use of bioscaffolds to study escape from tumor dormancy
Authors: Sprenger Cynthia C. , Long Thomas , Ratner Buddy , Plymate Stephen 
Published: August 2012

Tumor dormancy and escape from dormancy remains an elusive mystery in cancer progression; clinically, escape from dormancy is thought to result in recurrent, aggressive disease. Over 70% of prostate cancer patients have disseminated tumor cells (DTCs) in their bone marrow at the time of primary treatment, yet less than 30% of those patients developed recurrent disease 5-15+ years post-initial treatment. Currently there are no good methods for studying tumor dormancy and escape from dormancy. Imaging studies using mouse models of dormancy and examination of DTCs from patients for gene signatures that may give clues to such dormancy are still in the early stages of development. Other tools for studying dormancy in vitro and in vivo need to be developed, especially for prostate cancer, in which no mouse models of dormancy currently exist. Here we present a study in which we implanted porous polyHEMA scaffolds pre-seeded with human prostate cells (benign, malignant or dormant) into athymic nude mice and compared growth to that in Matrigel. The malignant line had similar growth curves in the pHEMA bioscaffold and Matrigel. Likewise the failure to grow in vivo for a benign prostate epithelial line was similar in Matrigel and the bioscaffold. However, while a human prostate cancer cell line engineered to overexpress the senescence-associated gene insulin-like growth factor binding protein 7 (IGFBP7), and thus mimic dormancy, failed to grow in vivo with Matrigel, it grew when placed in a pHEMA bioscaffold. Because of this difference in growth, we further explored the BP7 expressing prostate cancer cell line. We measured the mRNA and protein levels of BP7 in the implants to determine if loss of BP7 would, in part, explain the growth of the BP7 cell line in the scaffolds. mRNA levels of BP7 were actually significantly higher in the pHEMA (growth group) compared to the Matrigel (non-growth group), p&lt;0.0001. Protein levels of BP7 were not significantly different between the groups, however, there was a trend for higher BP7 expression in the pHEMA group. Angiogenesis is important in metastatic spread and growth, however, there were no significant differences in vessel density between the Matrigel and bioscaffold implants. Other factors that influence metastasis include activation of immune cells; in particular, macrophages are hypothesized to play an important role in metastasis. We stained the implants for macrophages and saw increased numbers of macrophages in the pHEMA implants compared with the Matrigel implants. We will present data from transcript profiles and cytokine antibody arrays that examine differences that occur between the dormant and growing BP7 prostate cancer implants. We hypothesize that infiltration of macrophages into bioscaffolds seeded with dormant cells creates a microenvironment that favors cancer cell escape from dormancy. Thus the use of pHEMA scaffolds provides an in vivo model for studying escape from dormancy in prostate cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5239. doi:1538-7445.AM2012-5239