B7-H6, an immunoligand for the natural killer cell activating receptor NKp30, reveals inhibitory effects on cell proliferation and migration, but not apoptosis, in cervical cancer derived-cell lines
Nehla Banu,
Annie Riera-Leal,
Jesse Haramati,
Pablo Cesar Ortiz-Lazareno,
Sandeep Surendra Panikar,
Blanca Estela Bastidas-Ramirez,
Gloria Yareli Gutierrez-Silerio,
Fabiola Solorzano-Ibarra,
Martha Cecilia Tellez-Bañuelos,
Jorge Gutierrez-Franco,
Miriam Ruth Bueno-Topete,
Ana Laura Pereira-Suarez,
Susana del Toro-Arreola
Affiliations
Nehla Banu
Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara
Annie Riera-Leal
Institute for Regenerative Cures, Department of Dermatology, University of California-Davis
Jesse Haramati
Laboratorio de Inmunobiología, Departamento de Biología Celular y Molecular, CUCBA, Universidad de Guadalajara
Pablo Cesar Ortiz-Lazareno
División de Inmunología, CIBO, Instituto Mexicano del Seguro Social
Sandeep Surendra Panikar
Centro de Física Aplicada y Tecnología Avanzada, Universidad Nacional Autónoma de México
Blanca Estela Bastidas-Ramirez
Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara
Gloria Yareli Gutierrez-Silerio
Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara
Fabiola Solorzano-Ibarra
Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara
Martha Cecilia Tellez-Bañuelos
Laboratorio de Inmunobiología, Departamento de Biología Celular y Molecular, CUCBA, Universidad de Guadalajara
Jorge Gutierrez-Franco
Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit
Miriam Ruth Bueno-Topete
Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara
Ana Laura Pereira-Suarez
Laboratorio de Inmunología, Departamento de Fisiología, CUCS, Universidad de Guadalajara
Susana del Toro-Arreola
Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara
Abstract Background Although great progress has been made in treatment regimens, cervical cancer remains as one of the most common cancer in women worldwide. Studies focusing on molecules that regulate carcinogenesis may provide potential therapeutic strategies for cervical cancer. B7-H6, an activating immunoligand expressed by several tumor cells, is known to activate NK cell-mediated cytotoxicity once engaged with its natural receptor NKp30. However, the opposite, that is, the effects in the tumor cell triggered by B7-H6 after interacting with NKp30 has not yet been well explored. Methods In this study, we evaluated the surface expression of B7-H6 by flow cytometry. Later, we stimulated B7-H6 positive cervical cancer derived-cell lines (HeLa and SiHa) with recombinant soluble NKp30 (sNKp30) protein and evaluated biological effects using the impedance RTCA system for cell proliferation, the scratch method for cell migration, and flow cytometry for apoptosis. Cellular localization of B7-H6 was determined using confocal microscopy. Results Notably, we observed that the addition of sNKp30 to the cervical cancer cell lines decreased tumor cell proliferation and migration rate, but had no effect on apoptosis. We also found that B7-H6 is selectively maintained in tumor cell lines, and that efforts to sort and purify B7-H6 negative or positive cells were futile, as negative cells, when cultured, regained the expression of B7-H6 and B7-H6 positive cells, when sorted and cultivated, lost a percentage of B7-H6 expression. Conclusions Our results suggest that B7-H6 has an important, as of yet undescribed, role in the biology of the cervical tumor cells themselves, suggesting that this protein might be a promising target for anti-tumor therapy in the future.
