STAT3 phosphorylation is required for the HepaCAM-mediated inhibition of castration-resistant prostate cancer cell viability and metastasis.
Animals
Cell Cycle Proteins
/ metabolism
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Cells, Cultured
Disease Models, Animal
Humans
Immunohistochemistry
Interleukins
/ metabolism
Lung Neoplasms
/ metabolism
Male
Mice
Neoplasm Metastasis
Phosphorylation
Prostatic Neoplasms, Castration-Resistant
/ metabolism
Recombinant Proteins
/ metabolism
STAT3 Transcription Factor
/ metabolism
Signal Transduction
/ drug effects
Treatment Outcome
Interleukin-22
CRPC
HepaCAM
metastasis
p-STAT3
viability
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
18
03
2021
received:
02
02
2021
accepted:
15
04
2021
pubmed:
29
4
2021
medline:
29
12
2021
entrez:
28
4
2021
Statut:
ppublish
Résumé
Castration-resistant prostate cancer (CRPC) is an advanced disease that is difficult to treat, the mechanism of it is unclear. This study illustrated the function of hepatocyte cell adhesion molecule (HepaCAM) on CRPC cell viability and metastasis. The expression of HepaCAM and p-STAT3 in CRPC tissues were determined by immunohistochemistry and western blot analysis. Cell Counting Kit-8 and colony formation assays were deployed to analyze the growth ability of CRPC cells following the adenovirus-mediated re-expression of HepaCAM. CRPC cell migration and invasion capacity were investigated by wound healing and Matrigel-coated transwell assays, respectively. The messenger RNA or protein levels of p-STAT3, CyclinD1, cMyc, MMP2, MMP9, and VEGF were determined by reverse transcription (RT) followed by quantitative real-time polymerase chain reaction (RT-qPCR), and western blot analysis after either HepaCAM re-expression alone or in combination with IL-22 treatment. A CRPC orthotopic xenograft mouse model was applied to investigate the functional effect of HepaCAM on the metastasis of CRPC cells to the lungs. The expression levels of HepaCAM were decreased while those of p-STAT3 were elevated in CRPC cells compare with surrounding benign tissues (p < .001). The overexpression of HepaCAM in CRPC cells notably reduced proliferation, migration, and invasion by inhibiting the expression of p-STAT3, CyclinD1, cMyc, MMP2, MMP9, and VEGF (p < .05). In addition, the expression of HepaCAM significantly inhibited the IL-22/p-STAT3 axis and the metastasis of CRPC cells to the lungs. Our data suggested that HepaCAM suppressed the viability of CRPC cells via the IL-22/p-STAT3 axis and inhibited the metastasis of CRPC cells from the prostate to the lungs (p < .05).
Sections du résumé
BACKGROUND
Castration-resistant prostate cancer (CRPC) is an advanced disease that is difficult to treat, the mechanism of it is unclear. This study illustrated the function of hepatocyte cell adhesion molecule (HepaCAM) on CRPC cell viability and metastasis.
METHODS
The expression of HepaCAM and p-STAT3 in CRPC tissues were determined by immunohistochemistry and western blot analysis. Cell Counting Kit-8 and colony formation assays were deployed to analyze the growth ability of CRPC cells following the adenovirus-mediated re-expression of HepaCAM. CRPC cell migration and invasion capacity were investigated by wound healing and Matrigel-coated transwell assays, respectively. The messenger RNA or protein levels of p-STAT3, CyclinD1, cMyc, MMP2, MMP9, and VEGF were determined by reverse transcription (RT) followed by quantitative real-time polymerase chain reaction (RT-qPCR), and western blot analysis after either HepaCAM re-expression alone or in combination with IL-22 treatment. A CRPC orthotopic xenograft mouse model was applied to investigate the functional effect of HepaCAM on the metastasis of CRPC cells to the lungs.
RESULTS
The expression levels of HepaCAM were decreased while those of p-STAT3 were elevated in CRPC cells compare with surrounding benign tissues (p < .001). The overexpression of HepaCAM in CRPC cells notably reduced proliferation, migration, and invasion by inhibiting the expression of p-STAT3, CyclinD1, cMyc, MMP2, MMP9, and VEGF (p < .05). In addition, the expression of HepaCAM significantly inhibited the IL-22/p-STAT3 axis and the metastasis of CRPC cells to the lungs.
CONCLUSIONS
Our data suggested that HepaCAM suppressed the viability of CRPC cells via the IL-22/p-STAT3 axis and inhibited the metastasis of CRPC cells from the prostate to the lungs (p < .05).
Substances chimiques
Cell Cycle Proteins
0
HEPACAM protein, human
0
Interleukins
0
Recombinant Proteins
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
603-611Informations de copyright
© 2021 Wiley Periodicals LLC.
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