Molecular Mechanism of Lymph Node Metastasis in Breast Cancer
Abstract
Many challenges exist in the current management of metastatic breast cancer as there are fewer recognized therapeutic strategies. Therefore, a better understanding of the molecular events in the metastatic process is critical. Several reports have described correlation of hyaluronan (HA) with initiation and progression of various types of epithelial cancers. The HA synthase (HAS) isoforms encode the enzymes that produce and deposit HA while the hyaluronidase (HYAL) genes code for enzymes that degrade HA and their expression is dysregulated in various tumors as a result of transcriptional and epigenetic changes that accompany progression. In this report, we examined the expression of HAS1, HAS2 and HAS3, HYAL1 and HYAL2 and LYVE1 in mammary tumor cell with different metastatic potential (4T1, highly metastatic; Cl66, moderately metastatic; Cl66M2, low metastatic). We observed increased expression of HAS1, HAS2 and HAS3 as well as HAYL 1 and HAYL2 in aggressive mammary tumor cells. Next we stably knocked-down HAS2 and HAS3 expression and overexpressed LYVE1 in 4T1 cells and analyzed cell proliferation, migration, tumor growth and metastasis. We observed that Has2/Has3 knock-down and LYVE1 overexpression modulated mammry tumor growth and spontaneous metastasis. Together, these data demonstrate an important role of HAS2 and LYVE1 in mammary tumor growth, angiogenesis, invasion, and metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2009
- Accession Number
- ADA518252
Entities
People
- R. K. Singh
Organizations
- University of Nebraska Omaha