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A switch from CD44⁺ cell to EMT cell drives the metastasis of prostate cancer.

Shang Z, Cai Q, Zhang M, Zhu S, Ma Y, Sun L, Jiang N, Tian J, Niu X, Chen J, Sun Y, Niu Y - Oncotarget (2015)

Bottom Line: Our results also suggested ADT might go through promoting TGFβ1-CD44 signaling to enhance swift to EMT.Targeting CD44 with salinomycin and siRNA could inhibit cell transition and decrease PCa invasion.Combined therapy of ADT with anti-CD44 may become a new potential therapeutic approach to battle later stage PCa.

View Article: PubMed Central - PubMed

Affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.

ABSTRACT
Epithelial-mesenchymal transition (EMT) has been linked to cancer stem-like (CD44+) cell in the prostate cancer (PCa) metastasis. However, the molecular mechanism remains elusive. Here, we found EMT contributed to metastasis in PCa patients failed in androgen deprivation therapy (ADT). Castration TRAMP model also proved PCa treated with ADT promoted EMT with increased CD44+ stem-like cells. Switched CD44+ cell to EMT cell is a key step for luminal PCa cell metastasis. Our results also suggested ADT might go through promoting TGFβ1-CD44 signaling to enhance swift to EMT. Targeting CD44 with salinomycin and siRNA could inhibit cell transition and decrease PCa invasion. Together, cancer stem-like (CD44+) cells could be the initiator cells of EMT modulated by TGFβ1-CD44 signaling. Combined therapy of ADT with anti-CD44 may become a new potential therapeutic approach to battle later stage PCa.

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Related in: MedlinePlus

CD44+ stem-like cells are responsible for mesenchymal transition and metastasis(a) The increasing expression of CK5 and CD44 in human CRPC samples comparing with hormone naïve PCa was demonstrated in IHC staining (three lanes on the left), immunofluorescence double staining of CK5 and CK8(the fourth lane from left), and immunofluorescence double staining of CD44 and CK8 (the fifth lane from left). (b) CD44+ and CD44− LNCaP cells were separated by MACS, their CD44, E-cadherin, N-cadherin and Vimentin expression were detected by real-time PCR. (c) CWR22rv1 cells were orthotopically implanted into the anterior lobes of nude mice prostate to generate xenograft tumors. CD44 expression in liver and diaphragm metastatic foci were compared to orthotopical xenograft tumors in IHC assay. Quantitation was shown in the right. Significance was defined as p<0.05(*).
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Figure 5: CD44+ stem-like cells are responsible for mesenchymal transition and metastasis(a) The increasing expression of CK5 and CD44 in human CRPC samples comparing with hormone naïve PCa was demonstrated in IHC staining (three lanes on the left), immunofluorescence double staining of CK5 and CK8(the fourth lane from left), and immunofluorescence double staining of CD44 and CK8 (the fifth lane from left). (b) CD44+ and CD44− LNCaP cells were separated by MACS, their CD44, E-cadherin, N-cadherin and Vimentin expression were detected by real-time PCR. (c) CWR22rv1 cells were orthotopically implanted into the anterior lobes of nude mice prostate to generate xenograft tumors. CD44 expression in liver and diaphragm metastatic foci were compared to orthotopical xenograft tumors in IHC assay. Quantitation was shown in the right. Significance was defined as p<0.05(*).

Mentions: Through the data from figure.5, we demonstrated that the increase of CK5 and CD44 expression were coincidently happened in CRPC samples comparing to those in human naïve specimens (Fig.5a, lane 1 and lane 3). And more importantly, CK5+/CK8+ (Fig.5a, lane 4) and CD44+/CK8+ (Fig.5a, lane 5) cells also increased in CRPC compared with those in hormone naïve. We further confirmed that CD44+ LNCaP cells expressed higher N-cadherin and Vimentin, with lower E-cadherin compared to those in CD44− LNCaP cells (Fig.5b). Furthermore, we also identified high CD44 expression in liver and diaphragm metastatic tumors comparing to the primary tumor of CWR22rv1 orthotopic xenografts (Fig.5c). Together, data from Fig.5 suggested that EMT like cell might be originated from PCa luminal cell (CK8+), which de-differentiated to CD44+/CK8+ cell, then acquired properties of mesenchymal, such as high expression of N-cadherin and Vimentin, combined with low expression of E-cadherin. This kind of CD44+ cancer stem like cell could be as an initiator of EMT like cell with the function of metastasis. Therefore, targeting CD44+ cancer stem like cell may decrease PCa EMT and metastasis.


A switch from CD44⁺ cell to EMT cell drives the metastasis of prostate cancer.

Shang Z, Cai Q, Zhang M, Zhu S, Ma Y, Sun L, Jiang N, Tian J, Niu X, Chen J, Sun Y, Niu Y - Oncotarget (2015)

CD44+ stem-like cells are responsible for mesenchymal transition and metastasis(a) The increasing expression of CK5 and CD44 in human CRPC samples comparing with hormone naïve PCa was demonstrated in IHC staining (three lanes on the left), immunofluorescence double staining of CK5 and CK8(the fourth lane from left), and immunofluorescence double staining of CD44 and CK8 (the fifth lane from left). (b) CD44+ and CD44− LNCaP cells were separated by MACS, their CD44, E-cadherin, N-cadherin and Vimentin expression were detected by real-time PCR. (c) CWR22rv1 cells were orthotopically implanted into the anterior lobes of nude mice prostate to generate xenograft tumors. CD44 expression in liver and diaphragm metastatic foci were compared to orthotopical xenograft tumors in IHC assay. Quantitation was shown in the right. Significance was defined as p<0.05(*).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359227&req=5

Figure 5: CD44+ stem-like cells are responsible for mesenchymal transition and metastasis(a) The increasing expression of CK5 and CD44 in human CRPC samples comparing with hormone naïve PCa was demonstrated in IHC staining (three lanes on the left), immunofluorescence double staining of CK5 and CK8(the fourth lane from left), and immunofluorescence double staining of CD44 and CK8 (the fifth lane from left). (b) CD44+ and CD44− LNCaP cells were separated by MACS, their CD44, E-cadherin, N-cadherin and Vimentin expression were detected by real-time PCR. (c) CWR22rv1 cells were orthotopically implanted into the anterior lobes of nude mice prostate to generate xenograft tumors. CD44 expression in liver and diaphragm metastatic foci were compared to orthotopical xenograft tumors in IHC assay. Quantitation was shown in the right. Significance was defined as p<0.05(*).
Mentions: Through the data from figure.5, we demonstrated that the increase of CK5 and CD44 expression were coincidently happened in CRPC samples comparing to those in human naïve specimens (Fig.5a, lane 1 and lane 3). And more importantly, CK5+/CK8+ (Fig.5a, lane 4) and CD44+/CK8+ (Fig.5a, lane 5) cells also increased in CRPC compared with those in hormone naïve. We further confirmed that CD44+ LNCaP cells expressed higher N-cadherin and Vimentin, with lower E-cadherin compared to those in CD44− LNCaP cells (Fig.5b). Furthermore, we also identified high CD44 expression in liver and diaphragm metastatic tumors comparing to the primary tumor of CWR22rv1 orthotopic xenografts (Fig.5c). Together, data from Fig.5 suggested that EMT like cell might be originated from PCa luminal cell (CK8+), which de-differentiated to CD44+/CK8+ cell, then acquired properties of mesenchymal, such as high expression of N-cadherin and Vimentin, combined with low expression of E-cadherin. This kind of CD44+ cancer stem like cell could be as an initiator of EMT like cell with the function of metastasis. Therefore, targeting CD44+ cancer stem like cell may decrease PCa EMT and metastasis.

Bottom Line: Our results also suggested ADT might go through promoting TGFβ1-CD44 signaling to enhance swift to EMT.Targeting CD44 with salinomycin and siRNA could inhibit cell transition and decrease PCa invasion.Combined therapy of ADT with anti-CD44 may become a new potential therapeutic approach to battle later stage PCa.

View Article: PubMed Central - PubMed

Affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.

ABSTRACT
Epithelial-mesenchymal transition (EMT) has been linked to cancer stem-like (CD44+) cell in the prostate cancer (PCa) metastasis. However, the molecular mechanism remains elusive. Here, we found EMT contributed to metastasis in PCa patients failed in androgen deprivation therapy (ADT). Castration TRAMP model also proved PCa treated with ADT promoted EMT with increased CD44+ stem-like cells. Switched CD44+ cell to EMT cell is a key step for luminal PCa cell metastasis. Our results also suggested ADT might go through promoting TGFβ1-CD44 signaling to enhance swift to EMT. Targeting CD44 with salinomycin and siRNA could inhibit cell transition and decrease PCa invasion. Together, cancer stem-like (CD44+) cells could be the initiator cells of EMT modulated by TGFβ1-CD44 signaling. Combined therapy of ADT with anti-CD44 may become a new potential therapeutic approach to battle later stage PCa.

Show MeSH
Related in: MedlinePlus