Abstract A03: Lymphocytes lead to circulating tumor cell death from 4D model seeded with non-metastatic lung cancer cell line

Abstract

Abstract Objective: Mouse lung cancer cell lines 393P and 344SQ are derived from KrasLA1/+ p53R172HΔG mice and have different metastatic potential in immunocompetent mice. 393P cells have local primary tumor growth but do not form metastatic lesions when injected into the subcutaneous space of 129sv mice. However, 344SQ cells form a primary tumor and metastatic lesions when injected into the subcutaneous space. Our aim is to determine if lymphocytes play a role in this differential metastatic lung cancer formation between the two cell lines. Methods: Both 393P and 344SQ cells were grown in the ex vivo 4D lung cancer model. We determined the amount of primary tumor growth, the number of circulating tumor cells (CTCs), and metastatic lesion formation. The CTCs from the 4D model seeded with either cells were injected into the tail veins of immunocompetent 129sv mice (wt) or immunodeficient mice (nu/nu). We calculated the Kaplan Meier survival curve. Next, we added lymphocytes derived from a 129sv mouse spleen to an ex vivo 4D lung cancer model seeded with 393P or 344SQ and isolated the CTCs. We plated the CTCs on a petri dish and compared the survival of these cells. Results: Both 393P and 344SQ cells grew in the 4D model. There were no significant differences in the primary tumor growth and circulating tumor cell formation between the two cell lines. There were no significant differences in the number of metastatic lesion formation between the two cell lines (p=0.5). When CTCs from the 4D model seeded with 344SQ were injected into the tail vein of nu/nu mice or wt mice, there were no differences in the survival rates between the two types of mice (p=0.3). However, nu/nu mice that were injected with CTC from the 4D model seeded with 393P were less likely to survive compared to the wt mice (p=0.002). No metastatic lesions formed in the wt mice injected with 393P CTC for 8 months. The CTC from the 4D model seeded with 344SQ and treated with lymphocytes had no significant difference in cell growth when cultured on a petri dish compared to the control group (p=0.9). However, the CTC from the 4D model seeded with 393P treated with lymphocytes had significantly less live cells compared to the control group (p=0.01). Conclusions: Lymphocytes inhibit metastatic lesion formation in 393P cell lines but not 344SQ cell lines. The ex vivo 4D lung cancer model allows for the identification of the cell type that is responsible for inhibition of metastasis. The model can be used to study the role of different components of a tumor's microenvironment in tumor metastasis. Citation Format: Dhruva K. Mishra, Humberto Juarez, Michael J. Thrall, Min P. Kim. Lymphocytes lead to circulating tumor cell death from 4D model seeded with non-metastatic lung cancer cell line. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A03.