Heterogenous expression of a murine B16 melanoma-associated antigen correlates with cell cycle |
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Authors: | Stanley P L Leong Philip D Noguchi Robert E Cunningham Tsuyoshi Takami Jack A Roth |
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Institution: | (1) Thoracic Oncology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, USA;(2) Division of Biochemistry and Biophysics, Office of Biologics Research Review, Center for Drugs and Biologics, FDA, 20892 Bethesda, Maryland, USA;(3) Department of Pathology, Sapporo Medical College, 060 Sapporo, Japan;(4) Department of Surgery and Arizona Cancer Center, The University of Arizona Health Sciences Center, College of Medicine, 85724 Tucson, Arizona, USA |
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Abstract: | Summary A murine monoclonal antibody (MM2-3C6) that reacts with a B16 murine melanoma-associated membrane antigen was used to study the relationship of antigen expression to the cell cycle. Dual-parameter flow cytometric measurements of membrane antigen and DNA revealed that antigen-positive cells were present throughout the cell cycle. Peak antigenic expression was noted during the late log phase of the cell growth curve with negligible antigen-negative population. The emergence of a distinct antigen-negative population (30%–40%) was noted in the late stationary phase. Cell cycle analysis indicated that the negative subpopulation was restricted to the G0/G1 phase, thus, demonstrating antigenic heterogeneity within the tumor cell population. Cell sorting was performed to analyze the origin of such heterogeneity. Following two sequential sortings, the antigen-negative cells became antigenic upon reculture. Again, at the late stationary phase, a distinct antigen-negative population (30%–40%) emerged. The sorted antigen-positive cells showed flow cytometric profiles identical to the sorted antigen-negative population upon reculture. Therefore, in this murine model, it appears that antigen expression is cell cycle dependent and such expression seems to be associated with proliferation. |
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