Differential growth and responsiveness to cancer therapy of tumor cells in different environments

Abstract

Tumor metastasis often confers poor prognosis for cancer patients due to lack of comprehensive strategy in dealing with cells growing in different environment. Current anticancer therapies have incomplete effectiveness because they were designed assuming metastatic tumors behave similarly in different organs. We hypothesize that tumors growing in different sites are biologically heterogeneous in growth potential, as well as in tumor response to anti-cancer therapies. To test this hypothesis, we have developed a multi-organ tumor growth model using the hydrodynamic cell delivery method to establish simultaneous and quantifiable tumor growth in the liver, lungs and kidneys of mice. We demonstrated that growth rate of melanoma tumor in the liver is higher than that of the lungs and kidneys. Tumors in the lungs and kidneys grew minimally at the early stage and aggressively thereafter. Tumors in different organs were also heterogeneous in response to chemotherapy and immune gene therapy using dacarbazine and interferon beta gene, respectively. Lung tumors responded to chemotherapy better than tumors in the liver, but showed minimal response to interferon beta gene therapy, compared to tumors in the liver and kidneys. We also confirmed differential tumor growth of the metastatic colon cancer in mice. Our results point out the importance of a better understanding of the differences in tumor growing in diverse environments. The biological heterogeneity of metastatic tumors demonstrated in this study necessitates establishing new drug screening strategies that take into account the environmental difference at the sites of tumor growth.