Prostate cancer progression into androgen independency is associated with alterations in cell adhesion and invasivity.
BACKGROUND
Mortality in prostate cancer is primarily due to failure to cure hormone refractory patients with metastatic disease. The present study focused on elucidating alterations in invasive properties, which are connected with progression into androgen independency.


METHODS
Ability to grow without anchor, migration, cell adhesion properties and expression of invasive factors were investigated in LNCaP and its androgen-independent subline LNCaP-19. Also, invasive capacity into blood vessels was examined in subcutaneous tumors.


RESULTS
Transition into an androgen-independent state was associated with ability to grow without anchor, increased migration, and alterations in cell adhesion properties. The tumor suppressor E-cadherin was downregulated and the proinvasive factors N-cadherin, MMP-9, and membrane type 1 (MT1)-MMP were upregulated in LNCaP-19. In addition, LNCaP-19 displayed a markedly increased invasivity into blood vessels.


CONCLUSIONS
The results show that LNCaP-19 mimics hormone refractory prostate cancer and therefore is an excellent tool for studies on androgen-independent cancer and invasion. This study shows that transition into an androgen-independent state correlates with several proinvasive alterations.
Jennbacken
Karin
K
Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Gustavsson
Heléne
H
Welén
Karin
K
Vallbo
Christina
C
Damber
Jan-Erik
JE
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D000728:Androgens; D015815:Cell Adhesion Molecules