Lymphoma cells contribute to the augmentation of plasma sL-selectins in the serum of lymphoma-bearing mice

Abstract

Like many integral membrane glycoproteins, the extracellular domain of L-selectin undergoes rapid shedding, which occurs on both resting and activated host leucocytes. Incubating normal or transformed leukocytes with phorbol esters can also artificially induce shedding of L-selectin, providing multiple possibilities for the source of soluble forms of L-selectin found in the serum of patients with hematological malignancies. Here, using genetically engineered L-selectin-deficient mouse models, we have measured the release of soluble circulating forms of L-selectin in the serum of lymphoma-bearing mice. We found that L-selectin-deficient lymphoma cells could not induce an elevation of circulating soluble forms of L-selectin in normal mice, as compared to lymphoma cells expressing L-selectin. Moreover, soluble forms of L-selectin were detected in the serum in mice bearing lymphoma induced by injection of T lymphoma cells expressing L-selectins. Interestingly, we also found that lymphoma cells that are unable to shed L-selectin in vitro following exposure to phorbol ester can generate soluble forms of serum L-selectin in vivo. Taken together, these results indicate that lymphoma cells are the major contributors to levels of soluble forms of L-selectins in lymphoma-bearing mice.

Keywords:

• Lymphoid leukemia
• cell lines and animal models
• lymphoma and hodgkin disease
• molecular genetics
• lymphocytes

Acknowledgments

The authors thank Diane Tremblay and Doris Legault for their excellent technical assistance and Dr. E.F. Potworowski for revision of the manuscript. This study was supported by a grant from the Cancer Research Society of Canada. C.A. is supported by a studentship from the National Science and Engineering Research Council of Canada and La Fondation Armand-Frappier. S.D.B. was supported by a Scholarship from the Canadian Institutes of Health Research and the Terry Fox Foundation through the National Cancer Institute of Canada. There are no conflicts of interest to disclose. Caroline Aubé performed research, analyzed data, and reviewed the paper; Simon D. Bélanger performed research and reviewed the article, and Yves St-Pierre designed research, analyzed data, and wrote the manuscript.