Objective:To establish a lung metastasis mouse model of clear cell renal cell carcinoma (CCRCC) and screen for lung metastasis CCRCC cell line,so as to lay a foundation for future study.Methods: RCC05-TXJ,a CCRCC cell line established by our lab,was used in the present study.The cells were proliferated and the cell suspension was subcutaneously injected into the NOD-SCID mice.The newly-formed tumors were transplanted into the renal capsule of NOD-SCID mice (in situ),and the formed tumors were harvested and again transplanted into NOD-SCID mice.A stable mouse model with CCRCC lung metastasis was established following several cycles of the transplantation.This transplantation cycle was repeated until the development of stable lung metastasis.The lung metastasis tissues were then injected into renal capsule for several cycles to induce the lung metastasis.The metastasis tissues were also primary cultured and proliferated and the cell suspensions were injected into renal capsule until the development of lung metastasis.The sub-cell lines which could stably produce lung metastasis were screened.During the screening,the in situ tumor information,lymphatic and pulmonary metastasis were all recorded in detail.Immunohistochemistry analyses were used to examine the expression of CA9 (a marker of renal cells) and CD133 (a marker of stem cells) on the metastatic CCRCC cells.Results: The lung metastasis was observed in the second cycle of the in situ transplantation of RCC05-TXJ in NOD-SCID mice.When the metastatic lung carcinoma tissues were used for in situ transplantation,lung metastasis was successfully established during the 3-6 cycles.CCRCC cells were successfully cultured with lung metastatic tissues,and the cell suspension of the passage 6 cells caused lung metastasis after implanted in the renal capsule.The result was stable in two repeated cycles.The lung metastatic RCC05-TXJ-L cells grew fast (average passage time was 2 days),and had a short in situ tumor-forming time (1 week).They also had a strong potential for lung metastasis and high expression of CA9 and CD133.Conclusion: Repeated in situ transplantation of RCC05-TXJ can be used to establish stable lung metastasis mice model of CCRCC.The selected RCC05-TXJ-L sub-cell line can stably induce lung metastasis in NOD-SCID mice.