PMID- 30808244
OWN - NLM
STAT- MEDLINE
DCOM- 20200512
LR  - 20200512
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 5
DP  - 2019 May
TI  - Integrin alpha11 in pancreatic stellate cells regulates tumor stroma interaction in 
      pancreatic cancer.
PG  - 6609-6621
LID - 10.1096/fj.201802336R [doi]
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the deadliest tumor due to its highly 
      abundant tumor stroma. Pancreatic stellate cells (PSCs) are considered precursor 
      cells of cancer-associated fibroblasts (CAFs), which induce tumor progression, 
      invasion, and metastasis. In this study, we investigated the role of integrin 
      subunit alpha (ITGA) 11, the receptor for collagen type I, in tumor stroma 
      interaction. Clinical sample analysis showed that ITGA11 was overexpressed by 
      CAFs in PDAC stroma, as shown with colocalization immunostaining with alpha-smooth 
      muscle actin. In contrast, there was no expression in healthy pancreas. Public 
      transcriptomic data confirmed a reduced expression of ITGA11 in healthy pancreas 
      and adjacent nontumoral tissues compared with human tumor tissues. Primary human 
      PSCs (hPSCs) activated with either TGF-beta or pancreatic cancer cell 
      (PANC-1)-conditioned medium (CM) resulted in the significant up-regulation of 
      ITGA11 and various CAF markers. Furthermore, short hairpin RNA (shRNA)-mediated 
      stable ITGA11 knockdown (shITGA11) in hPSCs significantly inhibited TGF-beta- and 
      PANC-1 CM-mediated activation at both gene and protein levels of extracellular 
      matrix, cytokines, and adhesion molecules. Additionally, shITGA11 hPSCs had a 
      reduced migration and contractility compared with shRNA control (shCTR) PSCs. 
      Furthermore, we investigated the effect of ITGA11 on the paracrine effects of 
      hPSCs. Interestingly, the CM from shITGA11 hPSCs, activated with either TGF-beta or 
      PANC-1 CM, caused tumor cells to migrate and invade lesser compared with their 
      counterpart, activated shCTR PSCs. In summary, this study presents ITGA11 as an 
      interesting stromal therapeutic target that plays a crucial role in the 
      regulation of the differentiation of PSCs into CAFs and paracrine 
      effects.-Schnittert, J., Bansal, R., Mardhian, D. F., van Baarlen, J., Ostman, 
      A., Prakash, J. Integrin alpha11 in pancreatic stellate cells regulates tumor stroma 
      interaction in pancreatic cancer.
FAU - Schnittert, Jonas
AU  - Schnittert J
AD  - Department of Biomaterials, Science, and Technology, TechMed Centre, Targeted 
      Therapeutics Section, Faculty of Science and Technology, University of Twente, 
      Enschede, The Netherlands.
FAU - Bansal, Ruchi
AU  - Bansal R
AD  - Department of Biomaterials, Science, and Technology, TechMed Centre, Targeted 
      Therapeutics Section, Faculty of Science and Technology, University of Twente, 
      Enschede, The Netherlands.
FAU - Mardhian, Deby F
AU  - Mardhian DF
AD  - Department of Biomaterials, Science, and Technology, TechMed Centre, Targeted 
      Therapeutics Section, Faculty of Science and Technology, University of Twente, 
      Enschede, The Netherlands.
FAU - van Baarlen, Joop
AU  - van Baarlen J
AD  - Laboratory Pathology East Netherlands (LabPON), Hengelo, The Netherlands.
FAU - Ostman, Arne
AU  - Ostman A
AD  - Department of Oncology-Pathology, Cancer Centre Karolinska, Karolinska 
      Institutet, Stockholm, Sweden.
FAU - Prakash, Jai
AU  - Prakash J
AD  - Department of Biomaterials, Science, and Technology, TechMed Centre, Targeted 
      Therapeutics Section, Faculty of Science and Technology, University of Twente, 
      Enschede, The Netherlands.
AD  - Department of Oncology-Pathology, Cancer Centre Karolinska, Karolinska 
      Institutet, Stockholm, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190226
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (ITGA11 protein, human)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Cancer-Associated Fibroblasts/metabolism/pathology
MH  - Carcinoma, Pancreatic Ductal/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Extracellular Matrix/*metabolism/pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Integrin alpha Chains/*metabolism
MH  - Male
MH  - Neoplasm Proteins/*metabolism
MH  - Pancreatic Neoplasms/*metabolism/pathology
MH  - Pancreatic Stellate Cells/*metabolism/pathology
MH  - *Tumor Microenvironment
OTO - NOTNLM
OT  - cancer-associated fibroblasts
OT  - cell migration
OT  - metastasis
OT  - transforming growth factor beta
OT  - tumor microenvironment
EDAT- 2019/02/28 06:00
MHDA- 2020/05/13 06:00
CRDT- 2019/02/28 06:00
PHST- 2019/02/28 06:00 [pubmed]
PHST- 2020/05/13 06:00 [medline]
PHST- 2019/02/28 06:00 [entrez]
AID - 10.1096/fj.201802336R [doi]
PST - ppublish
SO  - FASEB J. 2019 May;33(5):6609-6621. doi: 10.1096/fj.201802336R. Epub 2019 Feb 26.