Expression of E-cadherin and specific CXCR3 isoforms impact each other in prostate cancer
BACKGROUND: Carcinoma cells shift between epithelial and mesenchymal phenotypes during cancer progression, as defined by surface presentation of the cell-cell cohesion molecule E-cadherin, affecting dissemination, progression and therapy responsiveness. Concomitant with the loss of E-cadherin during the mesenchymal transition, the predominant receptor isoform for ELR-negative CXC ligands shifts from CXCR3-B to CXCR3-A which turns this classical G-protein coupled receptor from an inhibitor to an activator of cell migration, thus promoting tumor cell invasiveness. We proposed that CXCR3 was not just a coordinately changed receptor but actually a regulator of the cell phenotype.
METHODS: Immunoblotting, immunofluorescence, quantitative real-time PCR and flow cytometry assays investigated the expression of E-cadherin and CXCR3 isoforms. Intrasplenic inoculation of human prostate cancer (PCa) cells with spontaneous metastasis to the liver analyzed E-cadherin and CXCR3-B expression during cancer progression in vivo.
RESULTS: We found reciprocal regulation of E-cadherin and CXCR3 isoforms. E-cadherin surface expression promoted CXCR3-B presentation on the cell membrane, and to a lesser extent increased its mRNA and total protein levels. In turn, forced expression of CXCR3-A reduced E-cadherin expression level, whereas CXCR3-B increased E-cadherin in PCa. Meanwhile, a positive correlation of E-cadherin and CXCR3-B expression was found both in experimental PCa liver micro-metastases and patients' tissue.
CONCLUSIONS: CXCR3-B and E-cadherin positively correlated in vitro and in vivo in PCa cells and liver metastases, whereas CXCR3-A negatively regulated E-cadherin expression. These results suggest that CXCR3 isoforms may play important roles in cancer progression and dissemination via diametrically regulating tumor's phenotype.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
Cell communication and signaling : CCS - 17(2019), 1 vom: 12. Dez., Seite 164 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ma, Bo [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.10.2020 Date Revised 22.10.2020 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12964-019-0489-1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM304322504 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM304322504 | ||
| 003 | DE-627 | ||
| 005 | 20231225114735.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12964-019-0489-1 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1014.xml |
| 035 | |a (DE-627)NLM304322504 | ||
| 035 | |a (NLM)31831069 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ma, Bo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Expression of E-cadherin and specific CXCR3 isoforms impact each other in prostate cancer |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.10.2020 | ||
| 500 | |a Date Revised 22.10.2020 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Carcinoma cells shift between epithelial and mesenchymal phenotypes during cancer progression, as defined by surface presentation of the cell-cell cohesion molecule E-cadherin, affecting dissemination, progression and therapy responsiveness. Concomitant with the loss of E-cadherin during the mesenchymal transition, the predominant receptor isoform for ELR-negative CXC ligands shifts from CXCR3-B to CXCR3-A which turns this classical G-protein coupled receptor from an inhibitor to an activator of cell migration, thus promoting tumor cell invasiveness. We proposed that CXCR3 was not just a coordinately changed receptor but actually a regulator of the cell phenotype | ||
| 520 | |a METHODS: Immunoblotting, immunofluorescence, quantitative real-time PCR and flow cytometry assays investigated the expression of E-cadherin and CXCR3 isoforms. Intrasplenic inoculation of human prostate cancer (PCa) cells with spontaneous metastasis to the liver analyzed E-cadherin and CXCR3-B expression during cancer progression in vivo | ||
| 520 | |a RESULTS: We found reciprocal regulation of E-cadherin and CXCR3 isoforms. E-cadherin surface expression promoted CXCR3-B presentation on the cell membrane, and to a lesser extent increased its mRNA and total protein levels. In turn, forced expression of CXCR3-A reduced E-cadherin expression level, whereas CXCR3-B increased E-cadherin in PCa. Meanwhile, a positive correlation of E-cadherin and CXCR3-B expression was found both in experimental PCa liver micro-metastases and patients' tissue | ||
| 520 | |a CONCLUSIONS: CXCR3-B and E-cadherin positively correlated in vitro and in vivo in PCa cells and liver metastases, whereas CXCR3-A negatively regulated E-cadherin expression. These results suggest that CXCR3 isoforms may play important roles in cancer progression and dissemination via diametrically regulating tumor's phenotype | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a CXCR3 variant | |
| 650 | 4 | |a CXCR3-B | |
| 650 | 4 | |a E-cadherin | |
| 650 | 4 | |a EMT | |
| 650 | 4 | |a MErT | |
| 650 | 4 | |a Prostate cancer; metastasis | |
| 650 | 7 | |a CXCR3 protein, human |2 NLM | |
| 650 | 7 | |a Cadherins |2 NLM | |
| 650 | 7 | |a Protein Isoforms |2 NLM | |
| 650 | 7 | |a Receptors, CXCR3 |2 NLM | |
| 700 | 1 | |a Khazali, Ahmad |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Hanshuang |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yuhan |e verfasserin |4 aut | |
| 700 | 1 | |a Wells, Alan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell communication and signaling : CCS |d 2003 |g 17(2019), 1 vom: 12. Dez., Seite 164 |w (DE-627)NLM143253794 |x 1478-811X |7 nnns |
| 773 | 1 | 8 | |g volume:17 |g year:2019 |g number:1 |g day:12 |g month:12 |g pages:164 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12964-019-0489-1 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 17 |j 2019 |e 1 |b 12 |c 12 |h 164 | ||