PMID- 29721158
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 27
DP  - 2018 Apr 10
TI  - Acquired resistance to temsirolimus is associated with integrin alpha7 driven 
      chemotactic activity of renal cell carcinoma in vitro.
PG  - 18747-18759
LID - 10.18632/oncotarget.24650 [doi]
AB  - The mechanistic target of the rapamycin (mTOR) inhibitor, temsirolimus, has 
      significantly improved the outcome of patients with renal cell carcinoma (RCC). 
      However, development of temsirolimus-resistance limits its effect and metastatic 
      progression subsequently recurs. Since integrin alpha7 (ITGA7) is speculated to 
      promote metastasis, this investigation was designed to investigate whether 
      temsirolimus-resistance is associated with altered ITGA7 expression in RCC cell 
      lines and modified tumor cell adhesion and invasion. Caki-1, KTCTL-26, and A498 
      RCC cell lines were driven to temsirolimus-resistance by exposing them to 
      temsirolimus over a period of 12 months. Subsequently, adhesion to human 
      umbilical vein endothelial cells, to immobilized fibronectin, or collagen was 
      investigated. Chemotaxis was evaluated with a modified Boyden chamber assay and 
      ITGA7 expression by flow cytometry and western blotting. Chemotaxis significantly 
      decreased in temsirolimus-sensitive cell lines upon exposure to low-dosed 
      temsirolimus, but increased in temsirolimus-resistant tumor cells upon reexposure 
      to the same temsirolimus dose. The increase in chemotaxis was accompanied by 
      elevated ITGA7 at the cell surface membrane with simultaneous reduction of 
      intracellular ITGA7. ITGA7 knock-down significantly diminished motility of 
      temsirolimous-sensitive cells but elevated chemotactic activity of 
      temsirolimus-resistant Caki-1 and KTCTL-26 cells. Therefore, ITGA7 appears 
      closely linked to adhesion and migration regulation in RCC cells. It is 
      postulated that temsirolimus-resistance is associated with translocation of ITGA7 
      from inside the cell to the outer surface. This switch forces RCC migration 
      forward. Whether ITGA7 can serve as an important target in combatting RCC 
      requires further investigation.
FAU - Engl, Tobias
AU  - Engl T
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
FAU - Rutz, Jochen
AU  - Rutz J
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
FAU - Maxeiner, Sebastian
AU  - Maxeiner S
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
FAU - Fanguen, Sorel
AU  - Fanguen S
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
FAU - Juengel, Eva
AU  - Juengel E
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
AD  - Current address: Department of Urology and Pediatric Urology, University Medical 
      Center Mainz, Mainz, Germany.
FAU - Koschade, Sebastian
AU  - Koschade S
AD  - Department of Medicine II, Hematology and Oncology, Goethe-University, Frankfurt 
      am Main, Germany.
FAU - Roos, Frederik
AU  - Roos F
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
FAU - Khoder, Wael
AU  - Khoder W
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
FAU - Tsaur, Igor
AU  - Tsaur I
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
AD  - Current address: Department of Urology and Pediatric Urology, University Medical 
      Center Mainz, Mainz, Germany.
FAU - Blaheta, Roman A
AU  - Blaheta RA
AD  - Department of Urology, Goethe-University, Frankfurt am Main, Germany.
LA  - eng
PT  - Journal Article
DEP - 20180410
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5922352
OTO - NOTNLM
OT  - ITGA7
OT  - chemotaxis
OT  - renal cell cancer
OT  - resistance
OT  - temsirolimus
COIS- CONFLICTS OF INTEREST The authors declare that they have no competing interests.
EDAT- 2018/05/04 06:00
MHDA- 2018/05/04 06:01
PMCR- 2018/04/10
CRDT- 2018/05/04 06:00
PHST- 2017/08/18 00:00 [received]
PHST- 2018/02/27 00:00 [accepted]
PHST- 2018/05/04 06:00 [entrez]
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2018/05/04 06:01 [medline]
PHST- 2018/04/10 00:00 [pmc-release]
AID - 24650 [pii]
AID - 10.18632/oncotarget.24650 [doi]
PST - epublish
SO  - Oncotarget. 2018 Apr 10;9(27):18747-18759. doi: 10.18632/oncotarget.24650. 
      eCollection 2018 Apr 10.