Novel signatures of cancer-associated fibroblasts

Benedek Bozõky, Andrii Savchenko, P. Csermely, T. Korcsmáros, Zoltán Dúl, Fredrik Pontén, Lászlõ Székely, George Klein

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Increasing evidence indicates the importance of the tumor microenvironment, in particular cancer-associated fibroblasts, in cancer development and progression. In our study, we developed a novel, visually based method to identify new immunohistochemical signatures of these fibroblasts. The method employed a protein list based on 759 protein products of genes identified by RNA profiling from our previous study, comparing fibroblasts with differential growth-modulating effect on human cancers cells, and their first neighbors in the human protein interactome. These 2,654 proteins were analyzed in the Human Protein Atlas online database by comparing their immunohistochemical expression patterns in normal versus tumor-associated fibroblasts. Twelve new proteins differentially expressed in cancer-associated fibroblasts were identified (DLG1, BHLHE40, ROCK2, RAB31, AZI2, PKM2, ARHGAP31, ARHGAP26, ITCH, EGLN1, RNF19A and PLOD2), four of them can be connected to the Rho kinase signaling pathway. They were further analyzed in several additional tumor stromata and revealed that the majority showed congruence among the different tumors. Many of them were also positive in normal myofibroblast-like cells. The new signatures can be useful in immunohistochemical analysis of different tumor stromata and may also give us an insight into the pathways activated in them in their true in vivo context. The method itself could be used for other similar analysis to identify proteins expressed in other cell types in tumors and their surrounding microenvironment.

Original languageEnglish
Pages (from-to)286-293
Number of pages8
JournalInternational Journal of Cancer
Volume133
Issue number2
DOIs
Publication statusPublished - Jul 15 2013

Fingerprint

Proteins
Neoplasms
Fibroblasts
rho-Associated Kinases
Tumor Microenvironment
Myofibroblasts
Atlases
Cancer-Associated Fibroblasts
Databases
RNA
Growth

Keywords

  • cancer associated fibroblasts
  • myofibroblasts
  • Rho kinase
  • tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Novel signatures of cancer-associated fibroblasts. / Bozõky, Benedek; Savchenko, Andrii; Csermely, P.; Korcsmáros, T.; Dúl, Zoltán; Pontén, Fredrik; Székely, Lászlõ; Klein, George.

In: International Journal of Cancer, Vol. 133, No. 2, 15.07.2013, p. 286-293.

Research output: Contribution to journalArticle

Bozõky, B, Savchenko, A, Csermely, P, Korcsmáros, T, Dúl, Z, Pontén, F, Székely, L & Klein, G 2013, 'Novel signatures of cancer-associated fibroblasts', International Journal of Cancer, vol. 133, no. 2, pp. 286-293. https://doi.org/10.1002/ijc.28035
Bozõky, Benedek ; Savchenko, Andrii ; Csermely, P. ; Korcsmáros, T. ; Dúl, Zoltán ; Pontén, Fredrik ; Székely, Lászlõ ; Klein, George. / Novel signatures of cancer-associated fibroblasts. In: International Journal of Cancer. 2013 ; Vol. 133, No. 2. pp. 286-293.
@article{1396a20004994bf1a31acb8eb2be2c8a,
title = "Novel signatures of cancer-associated fibroblasts",
abstract = "Increasing evidence indicates the importance of the tumor microenvironment, in particular cancer-associated fibroblasts, in cancer development and progression. In our study, we developed a novel, visually based method to identify new immunohistochemical signatures of these fibroblasts. The method employed a protein list based on 759 protein products of genes identified by RNA profiling from our previous study, comparing fibroblasts with differential growth-modulating effect on human cancers cells, and their first neighbors in the human protein interactome. These 2,654 proteins were analyzed in the Human Protein Atlas online database by comparing their immunohistochemical expression patterns in normal versus tumor-associated fibroblasts. Twelve new proteins differentially expressed in cancer-associated fibroblasts were identified (DLG1, BHLHE40, ROCK2, RAB31, AZI2, PKM2, ARHGAP31, ARHGAP26, ITCH, EGLN1, RNF19A and PLOD2), four of them can be connected to the Rho kinase signaling pathway. They were further analyzed in several additional tumor stromata and revealed that the majority showed congruence among the different tumors. Many of them were also positive in normal myofibroblast-like cells. The new signatures can be useful in immunohistochemical analysis of different tumor stromata and may also give us an insight into the pathways activated in them in their true in vivo context. The method itself could be used for other similar analysis to identify proteins expressed in other cell types in tumors and their surrounding microenvironment.",
keywords = "cancer associated fibroblasts, myofibroblasts, Rho kinase, tumor microenvironment",
author = "Benedek Boz{\~o}ky and Andrii Savchenko and P. Csermely and T. Korcsm{\'a}ros and Zolt{\'a}n D{\'u}l and Fredrik Pont{\'e}n and L{\'a}szl{\~o} Sz{\'e}kely and George Klein",
year = "2013",
month = "7",
day = "15",
doi = "10.1002/ijc.28035",
language = "English",
volume = "133",
pages = "286--293",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Novel signatures of cancer-associated fibroblasts

AU - Bozõky, Benedek

AU - Savchenko, Andrii

AU - Csermely, P.

AU - Korcsmáros, T.

AU - Dúl, Zoltán

AU - Pontén, Fredrik

AU - Székely, Lászlõ

AU - Klein, George

PY - 2013/7/15

Y1 - 2013/7/15

N2 - Increasing evidence indicates the importance of the tumor microenvironment, in particular cancer-associated fibroblasts, in cancer development and progression. In our study, we developed a novel, visually based method to identify new immunohistochemical signatures of these fibroblasts. The method employed a protein list based on 759 protein products of genes identified by RNA profiling from our previous study, comparing fibroblasts with differential growth-modulating effect on human cancers cells, and their first neighbors in the human protein interactome. These 2,654 proteins were analyzed in the Human Protein Atlas online database by comparing their immunohistochemical expression patterns in normal versus tumor-associated fibroblasts. Twelve new proteins differentially expressed in cancer-associated fibroblasts were identified (DLG1, BHLHE40, ROCK2, RAB31, AZI2, PKM2, ARHGAP31, ARHGAP26, ITCH, EGLN1, RNF19A and PLOD2), four of them can be connected to the Rho kinase signaling pathway. They were further analyzed in several additional tumor stromata and revealed that the majority showed congruence among the different tumors. Many of them were also positive in normal myofibroblast-like cells. The new signatures can be useful in immunohistochemical analysis of different tumor stromata and may also give us an insight into the pathways activated in them in their true in vivo context. The method itself could be used for other similar analysis to identify proteins expressed in other cell types in tumors and their surrounding microenvironment.

AB - Increasing evidence indicates the importance of the tumor microenvironment, in particular cancer-associated fibroblasts, in cancer development and progression. In our study, we developed a novel, visually based method to identify new immunohistochemical signatures of these fibroblasts. The method employed a protein list based on 759 protein products of genes identified by RNA profiling from our previous study, comparing fibroblasts with differential growth-modulating effect on human cancers cells, and their first neighbors in the human protein interactome. These 2,654 proteins were analyzed in the Human Protein Atlas online database by comparing their immunohistochemical expression patterns in normal versus tumor-associated fibroblasts. Twelve new proteins differentially expressed in cancer-associated fibroblasts were identified (DLG1, BHLHE40, ROCK2, RAB31, AZI2, PKM2, ARHGAP31, ARHGAP26, ITCH, EGLN1, RNF19A and PLOD2), four of them can be connected to the Rho kinase signaling pathway. They were further analyzed in several additional tumor stromata and revealed that the majority showed congruence among the different tumors. Many of them were also positive in normal myofibroblast-like cells. The new signatures can be useful in immunohistochemical analysis of different tumor stromata and may also give us an insight into the pathways activated in them in their true in vivo context. The method itself could be used for other similar analysis to identify proteins expressed in other cell types in tumors and their surrounding microenvironment.

KW - cancer associated fibroblasts

KW - myofibroblasts

KW - Rho kinase

KW - tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=84877815243&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877815243&partnerID=8YFLogxK

U2 - 10.1002/ijc.28035

DO - 10.1002/ijc.28035

M3 - Article

VL - 133

SP - 286

EP - 293

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 2

ER -