Abstract 4128: Extensive morphological heterogeneity of circulating and selected high metastatic variants and differential chemosensitivity of human prostate cancer in mouse models

Abstract

Abstract Circulating PC-3-GFP human prostate cancer cells were collected from the blood from nude mice orthotopically implanted with PC-3-GFP. In parallel experiments, a highly metastatic PC-3-GFP cell line was developed by injecting parental PC-3-GFP to the footpad of nude mice which metastasized to inguinal lymph nodes from which the cancer cells were collected and were re-injected to the footpad. After 6 cycles, the PC-3-GFP cells collected from inguinal lymph nodes (PC-3-GFP-LN) and were injected to the footpad. PC-3-GFP-LN showed 100% metastasis to major lymph nodes (popliteal, inguinal, axillary, and cervical), and 100% metastasis to bone and lung. PC-3-GFP-CTC and PC-3-GFP-LN were cultured in vitro, and their morphology and chemo-sensitivity were comparing to the parental PC-3-GFP cells. Highly pleomorphic subpopulations of prostate cancer cells were identified in PC-3-GFP-CTC and PC-3-GFP-LN. The different cell subtypes included characteristic high malignancy features such as high nucleus to cytoplasmic (N/C) ratios and giant cell formation as a result of abnormal mitoses. Variations in growth rate, plating efficiency, size, shape, and number of the nuclei and nucleoli were observed. The results suggest extensive tumor heterogeneity in both sublines. The giant cells, contain multiple nuclei, cannot survive by themselves and need small cells around them in order to proliferate. However, giant cells also can produce smaller cells, which divide further. The ratio of giant cells/total cells were significantly higher in PC-3-GFP-LN compared to parental cells. However, the morphology of cells from lung metastasis and bone metastasis showed lung and bone epithelial features such as squamous on shape and tightly packed together. PC-3-GFP-CTC had similar sensitivity to both cisplatinum and docetaxel when compared to PC-3-parental cells. PC-3-GFP-LN was resistant. In contrast, PC-3-GFP-LN was sensitive to the traditional Chinese medicine (TCM) herbal mixture LQ similar to the parental cells. These results demonstrate that circulating tumor cells (CTCs) and selected high metastatic variants can be extensively heterogeneous and have different chemosensitivity profiles, suggesting new approaches to treatment such as with TCM. Citation Format: Lei Zhang, Chengyu Wu, Robert. M Hoffman. Extensive morphological heterogeneity of circulating and selected high metastatic variants and differential chemosensitivity of human prostate cancer in mouse models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4128. doi:10.1158/1538-7445.AM2015-4128