Fn14 receptor promotes invasive potential and metastatic capacity of non-small lung adenocarcinoma cells through the up-regulation of integrin α6

Jana Jandova, C. J. Mason, S. C. Pawar, George S Watts

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Lung cancer is one of the leading cause of cancer-related death around the world with the majority of diagnoses being non-small cell lung cancer (NSCLC). Given the poor survival rate and efficacy of current therapy for NSCLC, there is a need to identify and develop new therapeutic targets for treatment. We have observed significantly up-regulated levels of Fn14 in clinical samples of lung cancer relative to normal adjacent tissue. However, the functional role of Fn14 in these tumors is not understood yet. We used RT-PCR to establish the Fn14 expression profile in various NSCLC cell lines. Using isogenic variants of H460 NSCLC cell line with low, intermediate and high Fn14 expression as a cellular model, we determined that increased levels of integrin α6 in cells over-expressing Fn14 is suggestive of an important role of α6β1-fn14 interactions in motility of lung carcinoma and formation of metastases. Enhanced levels of Fn14 correlated with higher tumor cell migration and invasion in an MMP-1 dependent manner. Cells over-expressing Fn14 showed increased in vivo tumor formation with metastatic capacity to lymph nodes, lungs and liver. Thus, this research may be a step toward developing improved treatment strategies for NSCLC by improved detection and inhibition of metastases.

Original languageEnglish (US)
Pages (from-to)41-52
Number of pages12
JournalNeoplasma
Volume62
Issue number1
DOIs
StatePublished - 2015

Fingerprint

Integrins
Non-Small Cell Lung Carcinoma
Up-Regulation
Lung Neoplasms
Neoplasms
Neoplasm Metastasis
Cell Line
Lung
Matrix Metalloproteinases
Cell Movement
Lymph Nodes
Adenocarcinoma of lung
Carcinoma
Polymerase Chain Reaction
Liver
Therapeutics
Research

Keywords

  • Fn14
  • H460 cells
  • Integrin α6
  • Motility
  • Non-small cell lung cancer
  • TNFRSF12A
  • Tumor formation and metastasis

ASJC Scopus subject areas

  • Cancer Research

Cite this

@article{5f8d67d1c1944d2f9970e6c49e3528df,
title = "Fn14 receptor promotes invasive potential and metastatic capacity of non-small lung adenocarcinoma cells through the up-regulation of integrin α6",
abstract = "Lung cancer is one of the leading cause of cancer-related death around the world with the majority of diagnoses being non-small cell lung cancer (NSCLC). Given the poor survival rate and efficacy of current therapy for NSCLC, there is a need to identify and develop new therapeutic targets for treatment. We have observed significantly up-regulated levels of Fn14 in clinical samples of lung cancer relative to normal adjacent tissue. However, the functional role of Fn14 in these tumors is not understood yet. We used RT-PCR to establish the Fn14 expression profile in various NSCLC cell lines. Using isogenic variants of H460 NSCLC cell line with low, intermediate and high Fn14 expression as a cellular model, we determined that increased levels of integrin α6 in cells over-expressing Fn14 is suggestive of an important role of α6β1-fn14 interactions in motility of lung carcinoma and formation of metastases. Enhanced levels of Fn14 correlated with higher tumor cell migration and invasion in an MMP-1 dependent manner. Cells over-expressing Fn14 showed increased in vivo tumor formation with metastatic capacity to lymph nodes, lungs and liver. Thus, this research may be a step toward developing improved treatment strategies for NSCLC by improved detection and inhibition of metastases.",
keywords = "Fn14, H460 cells, Integrin α6, Motility, Non-small cell lung cancer, TNFRSF12A, Tumor formation and metastasis",
author = "Jana Jandova and Mason, {C. J.} and Pawar, {S. C.} and Watts, {George S}",
year = "2015",
doi = "10.4149/neo_2015_006",
language = "English (US)",
volume = "62",
pages = "41--52",
journal = "Neoplasma",
issn = "0028-2685",
publisher = "Vydavatel'stvo Slovenkej Akademie Vied/Veda Publishing House of the Slovak Academy of Sciences",
number = "1",

}

TY - JOUR

T1 - Fn14 receptor promotes invasive potential and metastatic capacity of non-small lung adenocarcinoma cells through the up-regulation of integrin α6

AU - Jandova, Jana

AU - Mason, C. J.

AU - Pawar, S. C.

AU - Watts, George S

PY - 2015

Y1 - 2015

N2 - Lung cancer is one of the leading cause of cancer-related death around the world with the majority of diagnoses being non-small cell lung cancer (NSCLC). Given the poor survival rate and efficacy of current therapy for NSCLC, there is a need to identify and develop new therapeutic targets for treatment. We have observed significantly up-regulated levels of Fn14 in clinical samples of lung cancer relative to normal adjacent tissue. However, the functional role of Fn14 in these tumors is not understood yet. We used RT-PCR to establish the Fn14 expression profile in various NSCLC cell lines. Using isogenic variants of H460 NSCLC cell line with low, intermediate and high Fn14 expression as a cellular model, we determined that increased levels of integrin α6 in cells over-expressing Fn14 is suggestive of an important role of α6β1-fn14 interactions in motility of lung carcinoma and formation of metastases. Enhanced levels of Fn14 correlated with higher tumor cell migration and invasion in an MMP-1 dependent manner. Cells over-expressing Fn14 showed increased in vivo tumor formation with metastatic capacity to lymph nodes, lungs and liver. Thus, this research may be a step toward developing improved treatment strategies for NSCLC by improved detection and inhibition of metastases.

AB - Lung cancer is one of the leading cause of cancer-related death around the world with the majority of diagnoses being non-small cell lung cancer (NSCLC). Given the poor survival rate and efficacy of current therapy for NSCLC, there is a need to identify and develop new therapeutic targets for treatment. We have observed significantly up-regulated levels of Fn14 in clinical samples of lung cancer relative to normal adjacent tissue. However, the functional role of Fn14 in these tumors is not understood yet. We used RT-PCR to establish the Fn14 expression profile in various NSCLC cell lines. Using isogenic variants of H460 NSCLC cell line with low, intermediate and high Fn14 expression as a cellular model, we determined that increased levels of integrin α6 in cells over-expressing Fn14 is suggestive of an important role of α6β1-fn14 interactions in motility of lung carcinoma and formation of metastases. Enhanced levels of Fn14 correlated with higher tumor cell migration and invasion in an MMP-1 dependent manner. Cells over-expressing Fn14 showed increased in vivo tumor formation with metastatic capacity to lymph nodes, lungs and liver. Thus, this research may be a step toward developing improved treatment strategies for NSCLC by improved detection and inhibition of metastases.

KW - Fn14

KW - H460 cells

KW - Integrin α6

KW - Motility

KW - Non-small cell lung cancer

KW - TNFRSF12A

KW - Tumor formation and metastasis

UR - http://www.scopus.com/inward/record.url?scp=84933514131&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84933514131&partnerID=8YFLogxK

U2 - 10.4149/neo_2015_006

DO - 10.4149/neo_2015_006

M3 - Article

AN - SCOPUS:84933514131

VL - 62

SP - 41

EP - 52

JO - Neoplasma

JF - Neoplasma

SN - 0028-2685

IS - 1

ER -