Related Experiment Videos
Endostatin expression by MDA-MB-435 breast cancer cells effectively inhibits tumor growth
Karen Liby1, Bonnie Neltner, Lisa Mohamet
1Department of Cell Biology, University of Cincinnati Medical School, Ohio 45267-0521, USA.
Abstract:
Tumors must induce the formation of new blood vessels in order to grow and metastasize. Endostatin, a cleaved product of collagen XVIII, inhibits endothelial cell proliferation and suppresses tumor growth and metastases. Several recent reports have questioned the efficacy of endostatin as a tumor suppressor in experimental animals. Our objective was to determine whether endostatin expression in breast cancer cells inhibits neovascularization and tumor growth in nude mice. MDA-MB-435 cells were transfected with an endostatin expression vector while control cells were transfected with an empty vector. Endostatin expression and secretion were confirmed by RT-PCR and a dot blot assay. No differences were observed in the growth rates of the endostatin-expressing and control clones in vitro. When injected into male and female nude mice, tumors from the control clones increased in size 10-15 fold over 8-10 weeks. In contrast, the endostatin clones formed small tumors which did not increase in size after the first 3 weeks. The endostatinderived tumors had a significantly higher apoptotic index (5.6%) compared to controls (2.0%) and showed a marked reduction in vascularization. In conclusion, expression of endostatin in MDA-MB-435 breast cancer cells effectively suppressed breast tumor growth by inhibiting angiogenesis and increasing apoptosis.
Insights
This study shows that endostatin, a collagen product, effectively suppresses breast tumor growth in mice by inhibiting new blood vessel formation (angiogenesis) and increasing cancer cell death (apoptosis).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tumor growth and metastasis depend on new blood vessel formation (angiogenesis).
- Endostatin, derived from collagen XVIII, is known to inhibit endothelial cell proliferation and suppress tumor growth.
- Recent studies have raised questions about endostatin's efficacy as a tumor suppressor in experimental models.
Purpose of the Study:
- To investigate whether endostatin expression in breast cancer cells inhibits neovascularization and tumor growth in vivo.
- To evaluate the anti-tumorigenic effects of endostatin in a mouse model.
Main Methods:
- Breast cancer cells (MDA-MB-435) were transfected with an endostatin expression vector or an empty control vector.
- Endostatin expression and secretion were confirmed using RT-PCR and dot blot assays.
- Tumor growth, vascularization, and apoptosis were assessed in nude mice injected with transfected cells.
Main Results:
- No significant difference in in vitro growth rates between endostatin-expressing and control cells.
- Endostatin-expressing tumors showed significantly suppressed growth in nude mice compared to controls.
- Endostatin-derived tumors exhibited reduced vascularization and a higher apoptotic index.
Conclusions:
- Endostatin expression in MDA-MB-435 breast cancer cells effectively suppresses tumor growth in vivo.
- The mechanism involves inhibition of angiogenesis and increased apoptosis within the tumor.
- Endostatin demonstrates significant potential as a therapeutic agent for breast cancer.