KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation

Kato, Kazuya; Noda, Takehiro; Kobayashi, Shogo; Sasaki, Kazuki; Iwagami, Yoshifumi; Yamada, Daisaku; Tomimaru, Yoshito; Takahashi, Hidenori; Uemura, Mamoru; Asaoka, Tadafumi; Shimizu, Junzo; Doki, Yuichiro; Eguchi, Hidetoshi

doi:https://doi.org/10.1111/cas.16144

KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation

Kato, Kazuya; Noda, Takehiro; Kobayashi, Shogo et al.

Cancer Science, 2024, 115(5), 1520-1535

Number of Access:2,051（2025-07-19 21:03 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/95644

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
CancerSci_115_5_1520	pdf	None	3.91 MB	83	2024.05.17

Creative Commons : Attribution - NonCommercial

Item Information

Output File Export EndNote Basic Export Mendeley

Title	KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation
Creator	CreatorName Kato, Kazuya
	NRID 1000050528594 1000050528594 researchmap permalink t-noda t-noda Scopus Author ID 12764559600 12764559600 ORCID 0000-0002-6768-5783 0000-0002-6768-5783 CreatorName Noda, Takehiro
	NRID 1000030452436 1000030452436 researchmap permalink 30452436 30452436 Scopus Author ID 7405376089 7405376089 ORCID 0000-0002-8828-1067 0000-0002-8828-1067 CreatorName Kobayashi, Shogo
	NRID 1000020745442 1000020745442 researchmap permalink Kazuki_Sasaki Kazuki_Sasaki Scopus Author ID 56087041900 56087041900 CreatorName Sasaki, Kazuki
	NRID 1000060597441 1000060597441 researchmap permalink yiwagami yiwagami Scopus Author ID 35074034100 35074034100 CreatorName Iwagami, Yoshifumi
	NRID 1000060571396 1000060571396 ORCID 0000-0002-6702-3800 0000-0002-6702-3800 researchmap permalink dyamada79222 dyamada79222 Scopus Author ID 37008067700 37008067700 CreatorName Yamada, Daisaku
	NRID 1000070528570 1000070528570 researchmap permalink yoshitotomimaru yoshitotomimaru Scopus Author ID 10240341100 10240341100 CreatorName Tomimaru, Yoshito
	NRID 1000090601120 1000090601120 ORCID 0000-0003-4801-3540 0000-0003-4801-3540 researchmap permalink hdnr_tkhs hdnr_tkhs Scopus Author ID 7405468781 7405468781 CreatorName Takahashi, Hidenori
	NRID 1000010528483 1000010528483 ORCID 0000-0001-6285-5619 0000-0001-6285-5619 researchmap permalink mamoruuemura mamoruuemura Scopus Author ID 36796497400 36796497400 CreatorName Uemura, Mamoru
	NRID 1000060528470 1000060528470 CreatorName Asaoka, Tadafumi
	CreatorName Shimizu, Junzo
	NRID 1000020291445 1000020291445 researchmap permalink ydoki3251 ydoki3251 Scopus Author ID 7006390687 7006390687 CreatorName Doki, Yuichiro
	NRID 1000090542118 1000090542118 researchmap permalink abcdabcdabcd abcdabcdabcd Scopus Author ID 7101627772 7101627772 CreatorName Eguchi, Hidetoshi
Subject	hepatectomy
	hypovascular tumor
	metastatic liver cancer
	prognosis
	tumorigenesis
Description	Kato K., Noda T., Kobayashi S., et al. KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. Cancer Science , (2024); https://doi.org/10.1111/cas.16144.
Abstract	Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM.
Publisher	John Wiley and Sons Inc
Source Title	Cancer Science
Volume (Issue)	115(5)
Page	1520-1535
Date of Issued	2024-05-01
Language	English
Handle URL	https://hdl.handle.net/11094/95644
PISSN	13479032
eISSN	13497006
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/cas.16144
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Cancer Science. 2024, 115(5), p. 1520-1535
DC.title	KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation
DC.creator	Kato, Kazuya
	Noda, Takehiro
	Kobayashi, Shogo
	Sasaki, Kazuki
	Iwagami, Yoshifumi
	Yamada, Daisaku
	Tomimaru, Yoshito
	Takahashi, Hidenori
	Uemura, Mamoru
	Asaoka, Tadafumi
	Shimizu, Junzo
	Doki, Yuichiro
	Eguchi, Hidetoshi
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-05-01
DC.identifier	https://doi.org/10.1111/cas.16144
DC.subject	hepatectomy
	hypovascular tumor
	metastatic liver cancer
	prognosis
	tumorigenesis
DC.description	Kato K., Noda T., Kobayashi S., et al. KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. Cancer Science , (2024); https://doi.org/10.1111/cas.16144.
DCTERMS.abstract	Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	95644
citation_title	KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation
citation_author	Kato, Kazuya
	Noda, Takehiro
	Kobayashi, Shogo
	Sasaki, Kazuki
	Iwagami, Yoshifumi
	Yamada, Daisaku
	Tomimaru, Yoshito
	Takahashi, Hidenori
	Uemura, Mamoru
	Asaoka, Tadafumi
	Shimizu, Junzo
	Doki, Yuichiro
	Eguchi, Hidetoshi
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2024-05-01
citation_journal_title	Cancer Science
citation_volume	115
citation_issue	5
citation_firstpage	1520
citation_lastpage	1535
citation_doi	https://doi.org/10.1111/cas.16144
citation_public_url	https://hdl.handle.net/11094/95644

KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation

Link to primary information

Item Information

Show details