Abstract/Summary:
Various types of endocrine therapy have been used for postmenopausal women with early stage breast
cancer. These therapies are safe and effective, but initially responsive breast tumors often develop resistance
and eventually recur. Since a communication between tumor and tumor circumstance plays an important role to
grow tumor and spread tumor to secondary organs, we examined the communication of endocrine resistant
breast cancer with stroma which is the part of a tissue or organ that has a connective and structural role in
cancer. We established four different endocrine resistant breast cancer cell lines and examined the
communication of these cells with four stromal cells. We found that CCL5 and endoglin might play an important
role in endocrine resistant breast cancer. Thus, we will 1) Investigate the role of CCL5 and endoglin in the
crosstalk between ERBC cells and stromal cells, 2) Unveil the mechanism of the upregulated CCL5 and endoglin
in crosstalk between ERBC and stroma, and 3) Develop therapeutic strategies to block the paracrine interaction
between the stromal cell and ERBC cell.
We will investigate which secreted factors could serve as a key regulator in the transition of breast cancer
cells to endocrine resistance and gaining of an aggressive phenotype. Further, secreted factors from the
communication between endocrine resistant breast cancer and stroma might prove to be an attractive target for
breast cancer drugs. Most of the cancer drugs in use currently have been developed to directly impact tumor
cells. These drugs do not do much to block signals coming from tumor circumstance. Our proposed investigation
will give us a small list of the most potent of these signals. Drugs, some of which we will identify here, and others
that will have to be developed, that block these signals could limit the ability of the tumors to spread to secondary
organs, which should result in overall survival gains for patients.