Abstract
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.
Highlights
Alterations in gene expression along with protein activation by cancer cells leads to transformation, proliferation, invasion, intravasation, dissemination in blood or lymphatic vessels, and eventually growth of distant metastases
green fluorescent protein (GFP)-labeled tumor cells were injected into rat mammary fat pads, and primary tumors were allowed to grow for 2 to 2.5 weeks
To provide insight into the pattern of gene expression associated with chemotactic and migratory carcinoma cells in vivo, we compared the gene expression profile of a subpopulation of tumor cells collected from the primary tumor by chemotaxis into a microneedle, called the invasive cells, with that of the general population of GFP-expressing tumor cells sorted from the whole primary tumor by Fluorescence-activated cell sorting (FACS) (Fig. 1)
Summary
Alterations in gene expression along with protein activation by cancer cells leads to transformation, proliferation, invasion, intravasation, dissemination in blood or lymphatic vessels, and eventually growth of distant metastases. We have shown that microarray-based gene expression studies can be successfully performed on cells collected by chemotaxis into microneedles held in the primary tumor [6].
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