Role of CD44 and Variants in Membrane-Cytoskeleton Interactions, Adhesion, Metastasis and Human Breast Cancers.
Abstract
CD44 isoforms belong to a family of cell adhesion molecules expressed on the cell surface of many tumor cells during human breast cancer progression. In this study we have analyzed the expression of CD44v3-containing isoforms CONTAINING HEPARIN SULFATE ADDITION SITES FOR GROWTH FACTOR BINDING in primary breast tumors, axillary nodal metastases and normal breast tissue. Using reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot, cloning, nucleotide sequencing and RT-in situ-PCR analyses, we have found that at least two CD44v3-containing isoforms, including one new species of CD44v2, delta v3-10 (delta v3 defined as a v3 exon lacking the first 24 base pairs) and another previously reported CD44v3, 8-10 are preferentially expressed in human primary breast tumor and axillary nodal metastases but not in normal breast tissues. These finding suggest that these CD44v3-containing isoforms are closely associated with breast cancer metastasis. Furthermore, we have established a stable transfection of CD44v2, delta v3-10 cDNA into non-metastatic human breast tumor cells (MCF-7) which contain endogenous CD44E isoform. Our results indicate that expression of CD44v2, delta v3-10 in MCF-7 cells promotes tumor cells undergo active cell migration. Treatments of MCF-7 transfectants expressing CD44v2, delta v3-10 with various agents such as anti-CD44v(sub 3) antibody, cytochalasin D (a microfilament disrupting agent known to prevent actin polymerization) and W-7 (a calmodulin antagonist) but not colchicine (a microtubule inhibitor), cause a significant inhibition of tumor cell migration. These findings suggest that CD44v2, delta v3-10 (related to human metastatic breast cancers) and associated microfilament components play an important role in the regulation of breast tumor cell migration required for the progression of human breast carcinomas.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA369294
Entities
People
- Lilly Y. Bourguignon
Organizations
- University of Miami