U-M Study: Herceptin Targets Breast Cancer Stem Cells
News Jul 10, 2008
A gene that is overexpressed in 20 percent of breast cancers increases the number of cancer stem cells, the cells that fuel a tumor's growth and spread, according to a new study from the University of Michigan Comprehensive Cancer Center.
The gene, HER2, causes cancer stem cells to multiply and spread, explaining why HER2 has been linked to a more aggressive type of breast cancer and to metastatic disease, in which the cancer has spread beyond the breast, the researchers say.
Further, the drug Herceptin, which is used to treat HER2-positive breast cancer, was found to target and destroy the cancer stem cells. Results of the study appear online in the journal Oncogene.
"This work suggests that the reason drugs that target HER2, such as Herceptin and Lapatanib, are so effective in breast cancer is that they target the cancer stem cell population. This finding provides further evidence for the cancer stem cell hypothesis," says study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.
The cancer stem cell hypothesis says that tumors originate in a small number of cells, called cancer stem cells, and that these cells are responsible for fueling a tumor’s growth. These cells represent fewer than 5 percent of the cells in a tumor. Wicha’s lab was part of the team that first identified stem cells in human breast cancer in 2003.
In the current study, researchers found that breast cancer cells overexpressing the HER2 gene had four to five times more cancer stem cells, compared to HER2-negative cancers. In addition, the HER2-positive cells caused the cancer stem cells to invade surrounding tissue, suggesting that HER2 is driving the invasiveness and spread of cancer.
The researchers then looked at the drug Herceptin, which is used to treat HER2-positive breast cancer. They found Herceptin reduced the number of cancer stem cells in the HER2-positive breast cancer cell lines by 80 percent, dropping it to the same levels seen in HER2-negative cell lines.
When HER2 was not overexpressed in the cell cultures, the researchers found, the cancer stem cell population did not increase. Nor did Herceptin have any effect on the HER2-negative cells, which is consistent with how Herceptin is used in the clinic.
"We are now studying what pathways are activated by HER2 overexpression. Our hope is that we could develop inhibitors of these pathways that might be effective in targeting cancer stem cells in women whose tumors do not overexpress HER2 or those who are resistant to Herceptin," says study author Hasan Korkaya, Ph.D., a U-M research fellow in internal medicine.
Switch Discovered to Convert Blood Vessels to Blood Stem Cells During Embryonic DevelopmentNews
Findings could aid research into creating new blood cells for transplants and understanding cancer metastasis.READ MORE
Unraveling How Mesenchymal Stem Cells From Gum Tissue Accelerate Wound HealingNews
To assist with wound healing, mesenchymal stem cells from the gum tissue secrete extracellular vesicles that contain the anti-inflammatory signaling molecule IL-1RA.READ MORE
Mending Broken Hearts with Cardiomyocyte MoldsNews
A team of researchers at Michigan Technological University in collaboration with Harvard Medical School, shows how cardiomyocytes grown in a heart-like environment mature more quickly, have improved functionality and are less likely to be rejected by patients’ bodies.READ MORE
Comments | 0 ADD COMMENT
World Congress on Advanced Pharmacy and Clinical Research
Jul 16 - Jul 17, 2018
6th Annual Congress on Biology and Medicine of Molecules
Sep 17 - Sep 18, 2018
International Conference on Molecular Biology and Stem Cells
Aug 13 - Aug 15, 2018
World Congress on Plant Science and Molecular Biology
Sep 12 - Sep 13, 2018