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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

ADT promotes the development of epithelial-mesenchymal transition (EMT) in PCa tumors(a) Immunohistochemical (IHC) analyses the expression of EMT markers, E-Cadherin, N-Cadherin and Vimentin in human PCa samples hormone naïve, after 3month ADT and of CRPC specimens. (b) TRAMP mice were castrated at 12-wk-old, and then analyzed the expression of E-Cadherin, N-Cadherin and Vimentin in 16, 20, and 24-wk-old TRAMP PCa samples by IHC (c) LNCaP cells are orthotopically implanted into the anterior lobes of nude mice to generate the LNCaP xenograft tumors. LNCaP xenograft tumors supplied with DHT were treated as androgen sensitive controls, meanwhile samples from castration tumors (3 days) and from castration re-growth CRPC tumors were examined. The expression of E-Cadherin, N-Cadherin and Vimentin were detected by IHC. The histologic analyses of human PCa specimens, TRAMP mice samples and LNCaP xenograft samples were quantitated by image-pro plus 6.0 software as shown in fig1. Significance was defined as p<0.05(*).
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Figure 1: ADT promotes the development of epithelial-mesenchymal transition (EMT) in PCa tumors(a) Immunohistochemical (IHC) analyses the expression of EMT markers, E-Cadherin, N-Cadherin and Vimentin in human PCa samples hormone naïve, after 3month ADT and of CRPC specimens. (b) TRAMP mice were castrated at 12-wk-old, and then analyzed the expression of E-Cadherin, N-Cadherin and Vimentin in 16, 20, and 24-wk-old TRAMP PCa samples by IHC (c) LNCaP cells are orthotopically implanted into the anterior lobes of nude mice to generate the LNCaP xenograft tumors. LNCaP xenograft tumors supplied with DHT were treated as androgen sensitive controls, meanwhile samples from castration tumors (3 days) and from castration re-growth CRPC tumors were examined. The expression of E-Cadherin, N-Cadherin and Vimentin were detected by IHC. The histologic analyses of human PCa specimens, TRAMP mice samples and LNCaP xenograft samples were quantitated by image-pro plus 6.0 software as shown in fig1. Significance was defined as p<0.05(*).

Mentions: We first compared PCa patients treated with ADT that already developed castration resistance (CRPC) vs those still sensitive to ADT treatment (ADPC) their EMT markers and found ADT-induced CRPC have altered EMT signaling with decreased E-Cadherin and increased N-cadherin and Vimentin (Fig.1a).


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)

ADT promotes the development of epithelial-mesenchymal transition (EMT) in PCa tumors(a) Immunohistochemical (IHC) analyses the expression of EMT markers, E-Cadherin, N-Cadherin and Vimentin in human PCa samples hormone naïve, after 3month ADT and of CRPC specimens. (b) TRAMP mice were castrated at 12-wk-old, and then analyzed the expression of E-Cadherin, N-Cadherin and Vimentin in 16, 20, and 24-wk-old TRAMP PCa samples by IHC (c) LNCaP cells are orthotopically implanted into the anterior lobes of nude mice to generate the LNCaP xenograft tumors. LNCaP xenograft tumors supplied with DHT were treated as androgen sensitive controls, meanwhile samples from castration tumors (3 days) and from castration re-growth CRPC tumors were examined. The expression of E-Cadherin, N-Cadherin and Vimentin were detected by IHC. The histologic analyses of human PCa specimens, TRAMP mice samples and LNCaP xenograft samples were quantitated by image-pro plus 6.0 software as shown in fig1. 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 1: ADT promotes the development of epithelial-mesenchymal transition (EMT) in PCa tumors(a) Immunohistochemical (IHC) analyses the expression of EMT markers, E-Cadherin, N-Cadherin and Vimentin in human PCa samples hormone naïve, after 3month ADT and of CRPC specimens. (b) TRAMP mice were castrated at 12-wk-old, and then analyzed the expression of E-Cadherin, N-Cadherin and Vimentin in 16, 20, and 24-wk-old TRAMP PCa samples by IHC (c) LNCaP cells are orthotopically implanted into the anterior lobes of nude mice to generate the LNCaP xenograft tumors. LNCaP xenograft tumors supplied with DHT were treated as androgen sensitive controls, meanwhile samples from castration tumors (3 days) and from castration re-growth CRPC tumors were examined. The expression of E-Cadherin, N-Cadherin and Vimentin were detected by IHC. The histologic analyses of human PCa specimens, TRAMP mice samples and LNCaP xenograft samples were quantitated by image-pro plus 6.0 software as shown in fig1. Significance was defined as p<0.05(*).
Mentions: We first compared PCa patients treated with ADT that already developed castration resistance (CRPC) vs those still sensitive to ADT treatment (ADPC) their EMT markers and found ADT-induced CRPC have altered EMT signaling with decreased E-Cadherin and increased N-cadherin and Vimentin (Fig.1a).

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