Introduction: Triple-negative breast cancers (TNBC) occur in 15-17% of patients, yet this subtype accounts for almost half of all breast cancer (BC) deaths. This breast cancer sub-type often occur in younger and African American (AA) women. TNBCs cannot be treated with current chemotherapies. Although initially responsive to chemotherapy, TNBCs tend to relapse and metastasize early. As there are no specific treatments for TNBCs, we aim to identify the therapeutic potential of insulin-like growth factor- 2 (IGF-2) in TNBC management.
Methods: Using immunohistochemistry archival breast tissue from women with metastatic TNBC was evaluated and scored for IGF-2 expression. To assess the ability of IGF-2 to stimulate cell proliferation and migration we used commercially available TNBC cell lines validated to be ER-alpha-negative (ER-), progesterone receptor-negative (PR-) and Her2 overexperssion-negative (HER2).
Results: We have found IGF-2 to be highly expressed archival breast tissue of women with metastatic TNBC. Using TNBC cell lines MDA-MB-231, HCC 38, HCC 1806 and HCC 1937, our in vitro studies demonstrate the ability of IGF-2 to stimulate TNBC proliferation and migration (P = 0.05). Further, the combination of NVP-AEW541, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, and BMS-754807, an inhibitor of IGF-1R and the insulin receptor (IR), cause a significant (P < 0.05) reduction in TNBC proliferation and migration. Investigation into the cellular characteristics of the TNBC cell lines used, suggest that BRCA1 mutations increase cell susceptibility to IGF-1R inhibitors.
Conclusion: Our data indicate that IGF-2 plays a role in TNBC metastasis, an action that can be inhibited by targeting multiple IGF-2 mediated receptors.
Citation Format: Nalo Hamilton, Diana Marquez-Garban, Richard Pietras. The insulin-like growth factor-2 (IGF-2): A potential therapeutic target for triple-negative breast cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5077.