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Targeting metastatic breast cancer with peptide epitopes derived from autocatalytic loop of Prss14/ST14 membrane serine protease and with monoclonal antibodies

DC Field Value Language
dc.contributor.authorKim, Ki Yeon-
dc.contributor.authorYoon, Minsang-
dc.contributor.authorCho, Youngkyung-
dc.contributor.authorLee, Kwang-Hoon-
dc.contributor.authorPark, Sora-
dc.contributor.authorLee, Se-ra-
dc.contributor.authorChoi, So-Young-
dc.contributor.authorLee, Deokjae-
dc.contributor.authorYang, Chansik-
dc.contributor.authorCho, Eun Hye-
dc.contributor.authorJeon, Sangjun Davie-
dc.contributor.authorKim, Seok-Hyung-
dc.contributor.authorKim, Chungho-
dc.contributor.authorKim, Moon Gyo-
dc.date.accessioned2019-11-06T23:33:30Z-
dc.date.available2019-11-07T08:43:39Z-
dc.date.issued2019-08-19-
dc.identifier.citationJournal of Experimental & Clinical Cancer Research, 38(1):363ko_KR
dc.identifier.issn1756-9966-
dc.identifier.urihttps://hdl.handle.net/10371/162625-
dc.description.abstractBackground
In order to develop a new immunotherapeutic agent targeting metastatic breast cancers, we chose to utilize autocatalytic feature of the membrane serine protease Prss14/ST14, a specific prognosis marker for ER negative breast cancer as a target molecule.

Methods
The study was conducted using three mouse breast cancer models, 4 T1 and E0771 mouse breast cancer cells into their syngeneic hosts, and an MMTV-PyMT transgenic mouse strain was used. Prss14/ST14 knockdown cells were used to test function in tumor growth and metastasis, peptides derived from the autocatalytic loop for activation were tested as preventive metastasis vaccine, and monoclonal and humanized antibodies to the same epitope were tested as new therapeutic candidates. ELISA, immunoprecipitation, Immunofluorescent staining, and flow cytometry were used to examine antigen binding. The functions of antibodies were tested in vitro for cell migration and in vivo for tumor growth and metastasis.

Results
Prss14/ST14 is critically involved in the metastasis of breast cancer and poor survival rather than primary tumor growth in two mouse models. The epitopes derived from the specific autocatalytic loop region of Prss14/ST14, based on structural modeling acted as efficient preventive metastasis vaccines in mice. A new specific monoclonal antibody mAb3F3 generated against the engineered loop structure could reduce cell migration, eliminate metastasis in PyMT mice, and can detect the Prss14/ST14 protein expressed in various human cancer cells. Humanized antibody huAb3F3 maintained the specificity and reduced the migration of human breast cancer cells in vitro.

Conclusion
Our study demonstrates that Prss14/ST14 is an important target for modulating metastasis. Our newly developed hybridoma mAbs and humanized antibody can be further developed as new promising candidates for the use in diagnosis and in immunotherapy of human metastatic breast cancer.
ko_KR
dc.description.sponsorshipThis work is supported in part by the National Research Foundation (NRF) grant funded by the Korea government (MEST) (No. 2013R1A1A2009892 and No. 2017R1A2B4008109) and Inha Univeristy Research Grant awarded to MGK and (No. 2015R1A2A1A15054021) to SHK.ko_KR
dc.language.isoenko_KR
dc.publisherBioMed Centralko_KR
dc.subjectPrss14ko_KR
dc.subjectMetastasisko_KR
dc.subjectImmunotherapyko_KR
dc.subjectCancer vaccineko_KR
dc.subjectAutocatalytic loopko_KR
dc.titleTargeting metastatic breast cancer with peptide epitopes derived from autocatalytic loop of Prss14/ST14 membrane serine protease and with monoclonal antibodiesko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor김기연-
dc.contributor.AlternativeAuthor윤민상-
dc.contributor.AlternativeAuthor조영경-
dc.contributor.AlternativeAuthor이광훈-
dc.contributor.AlternativeAuthor박소라-
dc.contributor.AlternativeAuthor이세라-
dc.contributor.AlternativeAuthor최소영-
dc.contributor.AlternativeAuthor이덕재-
dc.contributor.AlternativeAuthor양찬식-
dc.contributor.AlternativeAuthor조은혜-
dc.contributor.AlternativeAuthor전상준-
dc.contributor.AlternativeAuthor김석형-
dc.contributor.AlternativeAuthor김충호-
dc.contributor.AlternativeAuthor김문교-
dc.identifier.doi10.1186/s13046-019-1373-y-
dc.language.rfc3066en-
dc.rights.holderThe Author(s).-
dc.date.updated2019-08-25T03:29:35Z-
Appears in Collections:
College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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