Language
English
Publication Date
6-18-2026
Journal
Molecular Therapy Oncology
DOI
10.1016/j.omton.2026.201207
PMID
42124952
PMCID
PMC13158586
PubMedCentral® Posted Date
4-18-2026
PubMedCentral® Full Text Version
Post-print
Abstract
There is a lack of approaches to detect and kill metastatic cells. As an agent for metastasis targeting, a cyclic peptide BLMP6 has been previously characterized. As a step toward translation, we designed AZDye555-labeled BLMP6 and demonstrated its homing to metastases of human MDA-MB-231 cells in mice. We show that 68Ga-radiolabeled BLMP6 can be used for the detection of MDA-MB-231 metastases. We designed a peptide-drug conjugate consisting of monomethyl auristatin E (MMAE) and BLMP6. We show that MMAE-BLMP6 kills MDA-MB-231 cells in cell culture and in vivo. In mouse models of lung metastases, treatment with MMAE-BLMP6 suppressed metastasis growth and improved survival. Based on BLMP6 similarity to latent transforming growth factor β binding protein 4 (LTBP4), we identified fibulin-4 as a BLMP6 target. We show that BLMP6 mimics the LTBP4 domain binding to fibulin-4 and selectively binds to fibulin-4 in vitro. Fibulin-4 knockout in cancer cells abrogated BLMP6 homing to lung metastases in mice. Fibulin-4 expression was found to be increased in invasive and metastatic human breast cancer and correlated with the binding of AZDye555-BLMP6 in human tissue sections. Our results suggest that fibulin-4 and BLMP6 may be further developed for the detection and targeting of metastatic human cancers.
Keywords
breast, cancer, metastasis, peptide, MMAE, drug, radiolabel, Ga imaging, fibulin-4, LTBP4
Published Open-Access
yes
Recommended Citation
Daquinag, Alexes C; Ghosh, Sukhen C; AghaAmiri, Solmaz; et al., "Fibulin-4 Expressed in Metastatic Breast Cancer Is a Target of Peptide-Based Imaging Probes and Experimental Therapeutics" (2026). The Brown Foundation: Institute of Molecular Medicine. 90.
https://digitalcommons.library.tmc.edu/molecular_med/90
Graphical Abstract