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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
The development and characterization of a natural killer cell-resistant human renal cell carcinoma cell line
M S Ernstoff1, E M Jaffee, T Oeler
1Department of Medicine, University of Pittsburgh, Pa.
Abstract:
Natural killer (NK) cells are large granular lymphocytes that are able to recognize and lyse a broad spectrum of transformed cells. We report one approach to identify NK surface recognition molecules on human tumor targets. A cloned renal cell carcinoma (RCC) cell line, 5117GB, sensitive to NK activity, was made NK-resistant (5117GBT) by exposure to peripheral blood mononuclear cells. Both cell lines were found to be sensitive to lymphokine-activated killer cells. Both 5117GB and 5117GBT were positive for laminin (25-33%), CD2 (LFA-3 receptor, 95-98%), CD54 (ICAM-1, 99-100%) and CD58 (LFA-3, 100%). 5117GB was positive for HLA-ABC while 5117GBT lost detectable HLA-ABC. F(ab')2 fragments of HLA-ABC were not able to block NK-mediated cytotoxicity of 5117GB. We identified 6 murine monoclonal antibodies that preferentially bind either to sensitive or resistant RCC cells. The role of each of the antigens recognized by these antibodies in NK-mediated lysis is being explored. The development of NK-sensitive and NK-resistant human solid tumor cell lines may allow further exploration of surface molecules involved with NK binding and lysis.
Insights
Researchers identified surface molecules involved in natural killer (NK) cell recognition of tumor cells. Developing resistant cell lines helps uncover targets for NK cell-based cancer therapies.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Natural killer (NK) cells are crucial for recognizing and eliminating transformed cells.
- Identifying specific NK cell surface recognition molecules on tumor targets is essential for understanding NK cell-mediated cytotoxicity.
- Renal cell carcinoma (RCC) is a significant malignancy where NK cell activity can play a role in immune surveillance.
Purpose of the Study:
- To develop an approach for identifying NK cell surface recognition molecules on human tumor targets.
- To investigate the differences in surface molecule expression between NK-sensitive and NK-resistant renal cell carcinoma (RCC) cell lines.
- To explore the role of identified antigens in NK-mediated lysis of tumor cells.
Main Methods:
- Generation of an NK-resistant RCC cell line (5117GBT) from an NK-sensitive line (5117GB) by exposure to peripheral blood mononuclear cells.
- Comparative analysis of cell surface marker expression (laminin, CD2, CD54, CD58, HLA-ABC) on both sensitive and resistant cell lines using flow cytometry.
- Utilizing murine monoclonal antibodies to identify and characterize novel antigens preferentially binding to either sensitive or resistant RCC cells.
Main Results:
- Both 5117GB and 5117GBT cell lines were sensitive to lymphokine-activated killer (LAK) cells.
- While both lines expressed laminin, CD2, CD54, and CD58, the resistant 5117GBT line lost detectable HLA-ABC expression compared to the sensitive 5117GB line.
- Six murine monoclonal antibodies were identified that differentially bind to sensitive or resistant RCC cells, suggesting potential roles in NK recognition.
Conclusions:
- The development of NK-sensitive and NK-resistant tumor cell lines provides a valuable model for dissecting NK cell recognition mechanisms.
- Differential expression of surface molecules, particularly HLA-ABC, may influence NK cell-mediated lysis of RCC.
- Further investigation of antigens recognized by the identified monoclonal antibodies is warranted to elucidate their role in NK cell binding and tumor cell lysis.
