Breast cancer cells isolated by chemotaxis from primary tumors show increased survival and resistance to chemotherapy.
In this study, we have collected a migratory population of carcinoma cells by chemotaxis to epidermal growth factor-containing microneedles held in the primary tumor. The collected cells were subjected to microarray analysis for differential gene expression. The results show that anti-apoptotic genes are up-regulated and pro-apoptotic genes are down-regulated coordinately in the migratory subpopulation. Induction of apoptosis by doxorubicin, cisplatin, and etoposide in these cells demonstrates that they exhibit a lower drug-induced apoptotic index and lower cell death compared with carcinoma cells of the whole tumor. Our study indicates, for the first time, the capability of using a rat alograft model for evaluating the apoptotic status of a migratory subpopulation of tumor cells and the ability to study their resistance to chemotherapeutic agents directly. In addition, these results indicate that tumor cells that are chemotactic and migratory in response to epidermal growth factor in the primary tumor have a survival advantage over stationary tumor cells.
Goswami
Sumanta
S
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. sgoswami@aecom.yu.edu
Wang
Weigang
W
Wyckoff
Jeffrey B
JB
Condeelis
John S
JS
D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002465:Cell Movement; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival; D002633:Chemotaxis; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness