Abstract
Human CD44 standard isoform cDNA (hCD44s) was transfected into sis-transformed Balb/c 3T3 cells and into ras-revertant IIIA4 cells (both tumorigenic but nonmetastatic). Transfectants were injected subcutaneously into athymic nude mice to elucidate the functional role of hCD44s over-expression in progression and metastasis. The transfectants (but not parental cells) were capable of lung micrometastasis and of binding exogenously-added hyaluronan. hCD44s protein expression was conserved in lung micrometastases suggesting that it may have been necessary for their formation. In contrast, no hCD44s protein was detected in large subcutaneous (s.c.) tumors but normal levels of murine CD44 were detected. A second round of tumor development, using these two tumor cell classes, demonstrated that hCD44s-nonexpressing s.c. tumor cells re-expressed it in lung micrometastases. Conversely, hCD44s-expressing lung micrometastatic cells, when injected into a second group of mice, downregulated hCD44s expression in order to grow sizable s.c. tumors. S.c. tumor cells still contained the hCD44s gene but its expression was inhibited by epigenetic mechanisms, one of which was shown to be methylation of the hCD44s gene. These studies demonstrate (a) opposing selective pressures on CD44s over-expression for s.c. tumor growth and for metastatic spread to the lung and (b) further credence for the significance of CD44 for metastatic spread of fibrosarcomas. Therefore, CD44s may be a critical component of the metastatic phenotype induced by specific oncogenes.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kogerman, P., Sy, MS. & Culp, L. Counter-selection for over-expressed human CD44s in primary tumors versus lung metastases in a mouse fibrosarcoma model. Oncogene 15, 1407–1416 (1997). https://doi.org/10.1038/sj.onc.1201306
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201306
Keywords
This article is cited by
-
Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development
Cancer and Metastasis Reviews (2008)
-
Recombinant CD44-HABD is a novel and potent direct angiogenesis inhibitor enforcing endothelial cell-specific growth inhibition independently of hyaluronic acid binding
Oncogene (2004)
-
Divergent Ewing's sarcoma EWS/ETS fusions confer a common tumorigenic phenotype on NIH3T3 cells
Oncogene (1999)