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Increased resistance to apoptosis by bone marrow CD34 + progenitor cells from tumor‐bearing mice
Author(s) -
Young M. Rita I.,
Wright Mark A.,
Lathers Deanne M.R.,
Messingham Kelly A.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990812)82:4<609::aid-ijc23>3.0.co;2-a
Subject(s) - progenitor cell , bone marrow , cd34 , progenitor , apoptosis , cancer research , medicine , pathology , biology , stem cell , microbiology and biotechnology , genetics
Tumors, such as the murine Lewis lung carcinoma (LLC), produce granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), which increases the proportion of CD34 + hematopoietic progenitor cells in the bone marrow and in the periphery. This increase in peripheral CD34 + cells had been attributed to the growth‐promoting and mobilizing effects of the tumor‐derived GM‐CSF. However, the possibility that the CD34 + cells of tumor bearers might have enhanced survival abilities had not been considered. The present studies showed a significant baseline level of apoptotic cells in short‐term (5‐day) cultures of normal CD34 + cells containing GM‐CSF plus stem cell factor (SCF), and a markedly greater level of apoptosis in cytokine‐deficient cultures. In contrast, CD34 + cells from tumor bearers did not undergo such levels of apoptosis, even in the absence of cytokines. This resistance to apoptosis could be conferred to normal CD34 + cells by culture with LLC‐conditioned medium. Studies to elucidate possible mechanisms for the resistance to apoptosis by tumor‐exposed CD34 + cells showed increased levels of the pro‐life gene product bcl‐2. Finally, the resistance of tumor‐exposed CD34 + cells to ligation of the Fas receptor, a known apoptotic trigger in hematopoietic cells, was compared with that of control CD34 + cultures. Whereas approximately half of the normal CD34 + cells underwent apoptosis in response to Fas ligation, the tumor‐exposed CD34 + cells resisted apoptosis, even though their surface Fas expression was greater than that of normal CD34 + cells. Thus, our results show that the increased level of CD34 + cells in tumor bearers is due not only to an increased growth and mobilization of CD34 + cells as previously thought, but also may be due to an increased resistance to apoptosis that is conferred by tumor‐derived products and is associated with increased expression of bcl‐2. Int. J. Cancer 82:609–615, 1999. © 1999 Wiley‐Liss, Inc.