One in eight women in the United States will develop
invasive breast cancer during their lifetime, with 20% to 50% of patients
experiencing metastasis. Of those patients with metastatic breast cancer, approximately
90% of patients will die from it. Consequently, an effective treatment to stop
the proliferation of breast cancer metastasis is urgently needed. The CX3CR1
chemokine receptor has been observed to be directly involved in the attachment
of breast cancer cells to the skeleton. Two small molecule antagonists, JMS-17-2
and JMS-68, have been developed to target the CX3CR1 receptor. In vitro studies in SCID murine models utilizing human MDA-MB-231 breast cancer
cells demonstrate that JMS-17-2 and JMS-68 impede metastasis. Significant
reduction in the number of additional metastatic lesions and limited overall metastatic
burden were observed after antagonist administration, however the mechanism by
which proliferation of metastatic tumors was slowed by these drugs is not yet understood.
In this study, effects of JMS-17-2 and JMS-68 on tumor cell proliferation was
evaluated by immunocytochemistry targeting Ki-67, a recognized marker for cell
proliferation, and bromodeoxyuridine (BrdU), an introduced thymidine analog
which indicates movement through the S-phase of the cell cycle. Ki-67 and BrdU
staining indicated that neither antagonist inhibits proliferation of MDA-MB-231
cells in vitro at various dose and
time points. Future work will aim to investigate other mechanisms by which the
antagonists interfere with the interaction between tumor cells and stroma
microenvironments to stop metastatic tumor progression.
