Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells

Taek Keun Kim; Chang Sik Park; Mee Hyun Jeoung; Woo Ran Lee; Nam Kyung Go; Jong Rip Choi; Tae Sup Lee; Hyunbo Shim; Sukmook Lee

doi:10.1016/j.bbrc.2015.11.031

Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells

Taek Keun Kim, Chang Sik Park, Mee Hyun Jeoung, Woo Ran Lee, Nam Kyung Go, Jong Rip Choi, Tae Sup Lee, Hyunbo Shim, Sukmook Lee

Department of Life Science

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Tetraspanin 8 (TSPAN8) is a tumor-associated antigen implicated in tumor progression and metastasis. However, the validation of TSPAN8 as a potential therapeutic target in metastatic colorectal cancer (mCRC) has not yet been studied. In this study, through several in vitro methodologies, we identified a large extracellular loop of TSPAN8 (TSPAN8-LEL) as a key domain for regulating mCRC invasion. Using phage display technology, we developed a novel anti-TSPAN8-LEL human antibody with subnanomolar affinity that specifically recognizes amino acids 140-205 of TSPAN8-LEL in a conformation-dependent manner. Finally, we demonstrated that the antibody specifically reduces invasion in the HCT116 and LoVo mCRC cell lines more potently than in the HCT-8 and SW480 non-mCRC cell lines. Our data suggest that TSPAN8-LEL may play an important role in mCRC cell invasion, and that the antibody we have developed could be a useful tool for inhibiting the invasion of TSPAN8-expressing mCRCs.

Original language	English
Pages (from-to)	774-780
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	468
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2015.11.031
State	Published - 25 Dec 2015

Bibliographical note

Funding Information:
This work was supported by an intramural research grant ( 10TS03 ) from Scripps Korea Antibody Institute in the Republic of Korea.

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

Keywords

Colorectal cancer cells
Human antibody
Invasion
Large extracellular loop
TSPAN8

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2015.11.031

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title = "Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells",

abstract = "Tetraspanin 8 (TSPAN8) is a tumor-associated antigen implicated in tumor progression and metastasis. However, the validation of TSPAN8 as a potential therapeutic target in metastatic colorectal cancer (mCRC) has not yet been studied. In this study, through several in vitro methodologies, we identified a large extracellular loop of TSPAN8 (TSPAN8-LEL) as a key domain for regulating mCRC invasion. Using phage display technology, we developed a novel anti-TSPAN8-LEL human antibody with subnanomolar affinity that specifically recognizes amino acids 140-205 of TSPAN8-LEL in a conformation-dependent manner. Finally, we demonstrated that the antibody specifically reduces invasion in the HCT116 and LoVo mCRC cell lines more potently than in the HCT-8 and SW480 non-mCRC cell lines. Our data suggest that TSPAN8-LEL may play an important role in mCRC cell invasion, and that the antibody we have developed could be a useful tool for inhibiting the invasion of TSPAN8-expressing mCRCs.",

keywords = "Colorectal cancer cells, Human antibody, Invasion, Large extracellular loop, TSPAN8",

author = "Kim, {Taek Keun} and Park, {Chang Sik} and Jeoung, {Mee Hyun} and Lee, {Woo Ran} and Go, {Nam Kyung} and Choi, {Jong Rip} and Lee, {Tae Sup} and Hyunbo Shim and Sukmook Lee",

note = "Funding Information: This work was supported by an intramural research grant ( 10TS03 ) from Scripps Korea Antibody Institute in the Republic of Korea. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc. All rights reserved.",

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doi = "10.1016/j.bbrc.2015.11.031",

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T1 - Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells

AU - Kim, Taek Keun

AU - Park, Chang Sik

AU - Jeoung, Mee Hyun

AU - Lee, Woo Ran

AU - Go, Nam Kyung

AU - Choi, Jong Rip

AU - Lee, Tae Sup

AU - Shim, Hyunbo

AU - Lee, Sukmook

N1 - Funding Information: This work was supported by an intramural research grant ( 10TS03 ) from Scripps Korea Antibody Institute in the Republic of Korea. Publisher Copyright: © 2015 Elsevier Inc. All rights reserved.

PY - 2015/12/25

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N2 - Tetraspanin 8 (TSPAN8) is a tumor-associated antigen implicated in tumor progression and metastasis. However, the validation of TSPAN8 as a potential therapeutic target in metastatic colorectal cancer (mCRC) has not yet been studied. In this study, through several in vitro methodologies, we identified a large extracellular loop of TSPAN8 (TSPAN8-LEL) as a key domain for regulating mCRC invasion. Using phage display technology, we developed a novel anti-TSPAN8-LEL human antibody with subnanomolar affinity that specifically recognizes amino acids 140-205 of TSPAN8-LEL in a conformation-dependent manner. Finally, we demonstrated that the antibody specifically reduces invasion in the HCT116 and LoVo mCRC cell lines more potently than in the HCT-8 and SW480 non-mCRC cell lines. Our data suggest that TSPAN8-LEL may play an important role in mCRC cell invasion, and that the antibody we have developed could be a useful tool for inhibiting the invasion of TSPAN8-expressing mCRCs.

AB - Tetraspanin 8 (TSPAN8) is a tumor-associated antigen implicated in tumor progression and metastasis. However, the validation of TSPAN8 as a potential therapeutic target in metastatic colorectal cancer (mCRC) has not yet been studied. In this study, through several in vitro methodologies, we identified a large extracellular loop of TSPAN8 (TSPAN8-LEL) as a key domain for regulating mCRC invasion. Using phage display technology, we developed a novel anti-TSPAN8-LEL human antibody with subnanomolar affinity that specifically recognizes amino acids 140-205 of TSPAN8-LEL in a conformation-dependent manner. Finally, we demonstrated that the antibody specifically reduces invasion in the HCT116 and LoVo mCRC cell lines more potently than in the HCT-8 and SW480 non-mCRC cell lines. Our data suggest that TSPAN8-LEL may play an important role in mCRC cell invasion, and that the antibody we have developed could be a useful tool for inhibiting the invasion of TSPAN8-expressing mCRCs.

KW - Colorectal cancer cells

KW - Human antibody

KW - Invasion

KW - Large extracellular loop

KW - TSPAN8

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Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells

Abstract

Bibliographical note

Keywords

UN SDGs

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