About 15 percent of breast cancer cases are classified as triple negative cancer in which no progesterone receptors, estrogen and Her2. These cancers do not respond to hormone therapy target, and, as a rule, are particularly aggressive, often fail to respond to chemotherapy and metastasize to other tissues.
Researchers have noted that patients with triple negative breast cancer patients who have an increased number of immune cells called myeloid suppressor cells (MLSK) had worse results. But it is still unclear how these cells contribute to the progression and spread of tumors.
A new report led by Professor of Biomedical Sciences of the University of Pennsylvania Rumeli Chakrabarti and Sushil Kumar, a doctoral student in the lab Chakrabarty, is dedicated to the relationship between MLSK and aggressive disease. Researchers have identified deltaNp63 protein on tumor cells, which direct MLSK in tumor and metastatic sites, where they contribute to tumor growth and metastasis. Blocking of the protein themselves or MLSK reduces tumor growth and metastasis in mouse model.
"We believe that our findings are important for patients with triple negative breast cancer - said Chakrabarti. - deltaNp63 can be used not only as a biomarker, but also as a target protein in addition to chemotherapy and radiation therapy. "
Earlier studies have shown that elevated levels of deltaNp63 associated with the occurrence of breast cancer. In the current work team has found that the protein level was increased in the primary tumor samples.
The researchers used several mouse models of transplantation and tissue to see how the change affects the level deltaNp63 cancer behavior, and found that lower levels correspond to fewer metastases in distant tissues. In addition, lower levels deltaNp63 made much less aggressive tumor and decreased the amount MLSK.
Researchers have confirmed the relationship between deltaNp63 and MLSK, showing that blocking the two signal molecules CXCL2 and CCL22, activated protein decreased metastases and the growth of blood vessels associated with tumor growth, while increasing the levels of these signaling molecules has led to the fact that MLSK increased growth.
"How immune cells help cancer cells? - said Chakrabarti. - I think they help cancer stem cells to grow faster. " Cancer stem cells can give rise to other cells in the tumor as well as normal stem cells can differentiate into other cell types. These cells are resistant to chemotherapy and radiation therapy, which may explain why patients with triple negative breast cancer patients do not respond to therapy.
The research team used small molecules to inhibit CXCL2 and CCL22 in human cell lines, as well as in a mouse model. Levels MLSK decreased, which significantly reduces the symptoms of metastasis.
Drugs aimed at MLSK can fill the gap in the treatment of breast cancer. Offered in conjunction with the general treatment, such as chemotherapy and radiotherapy, it opens up new possibilities of treatment. Now the lab is working with animal models and cell lines derived from patients with cancer, to test this combined approach to treatment.