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A novel peptide that directs chemotherapy against breast cancer stem cell
Author(s) -
Lee Andy,
Lee TeWei,
Yu John,
Wu HanChung,
Yu Alice
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.629.18
Subject(s) - cd44 , cancer research , peptide , breast cancer , cancer stem cell , stem cell , in vivo , cancer cell , chemotherapy , chemistry , cancer , cell , medicine , biology , biochemistry , microbiology and biotechnology
L‐peptide was previously selected for its ability to bind nasopharyngeal cancer through unknown targets. Herein, we identified GRP78 as the target protein of L‐peptide and demonstrated their direct interaction using purified cell surface form of GRP78. Interestingly, L‐peptide displayed a broad spectrum of binding to a wide variety of cancers including breast cancers. Importantly, binding of L‐peptide to breast cancer clinical specimens and breast cancer stem cells (BCSC) (CD44 + /CD24 ‐ ) prompted us to investigate its potential as a targeting agent for delivering chemotherapeutic agents in vivo . Treatment of mice bearing breast cancer patient derived xenografts (PDX) with L‐peptide‐conjugated lipodox (LD‐L) resulted in significantly greater suppression of tumor growth than lipodox (LD). Analyses of residual tumors showed that LD‐L but not LD reduced the BCSC subpopulation. Treated tumor cells were re‐implanted into mice to create a second‐generation model of PDX ( 2ND PDX) that were subsequently subjected to the same treatment regimen. Notably, 2ND PDX treated with LD‐L showed not only further suppression in tumor growth rate, tumor size, mammosphere formation but also significantly delayed the initiation of tumor when compared to that of 2ND PDX treated with LD or PBS. Most importantly, BCSC subpopulation was further reduced in the LD‐L‐treated 2ND PDX. Moreover, L‐peptide‐conjugated liposomes encapsulating isotope 188 Re was able to detect tumor on xenograft models using microSPECT. Taken together, our results implicated L‐peptide as a potential cancer‐targeting agent for chemotherapy, tumor imaging, and radiotherapy.