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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 is a poor prognosis marker of localized PCa(a) CD44 expression in low-, medium-, and high-risk of human PCa was analyzed in IHC staining. (b &c) The expression levels of CD44 in 118 PCa patient samples were analyzed. A cut-off value of 10% was determined from the receiver operating characteristic (ROC) curve. Low and high CD44 staining were related to the disease risk but not age. (d & e) Kaplan-Meier curve analyzed the relationship between expression level of CD44 and biochemical recurrence or distant metastasis. Significance was defined as p<0.05(*) (f) Summarize the mechanism of ADT enhanced prostate cancer metastasis via alternation the TGFβ1-CD44 signaling.
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Figure 7: CD44 is a poor prognosis marker of localized PCa(a) CD44 expression in low-, medium-, and high-risk of human PCa was analyzed in IHC staining. (b &c) The expression levels of CD44 in 118 PCa patient samples were analyzed. A cut-off value of 10% was determined from the receiver operating characteristic (ROC) curve. Low and high CD44 staining were related to the disease risk but not age. (d & e) Kaplan-Meier curve analyzed the relationship between expression level of CD44 and biochemical recurrence or distant metastasis. Significance was defined as p<0.05(*) (f) Summarize the mechanism of ADT enhanced prostate cancer metastasis via alternation the TGFβ1-CD44 signaling.

Mentions: Due to CD44+ cell population increased was one of essential conditions for EMT in CRPC, we further detected whether expression of CD44 was correlated with prognosis in clinic. The expression of CD44 was analyzed in 118 PCa patient samples. A cut-off value of 10% was determined from the receiver operating characteristic (ROC) curve, and according to this value, two groups (low and high CD44 staining) were assigned. The high level expression of CD44 was significantly related to the disease risk but not in age subgroup (Fig.7a-c). Kaplan-Meier curve was addressed to evaluate the role of CD44 as a prognosis marker, showing that high expression level of CD44 was associated with biochemical recurrence and distant metastasis (Fig.7d&7e). The above clinical data suggested that CD44 may become a poor prognosis marker of PCa.


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 is a poor prognosis marker of localized PCa(a) CD44 expression in low-, medium-, and high-risk of human PCa was analyzed in IHC staining. (b &c) The expression levels of CD44 in 118 PCa patient samples were analyzed. A cut-off value of 10% was determined from the receiver operating characteristic (ROC) curve. Low and high CD44 staining were related to the disease risk but not age. (d & e) Kaplan-Meier curve analyzed the relationship between expression level of CD44 and biochemical recurrence or distant metastasis. Significance was defined as p<0.05(*) (f) Summarize the mechanism of ADT enhanced prostate cancer metastasis via alternation the TGFβ1-CD44 signaling.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: CD44 is a poor prognosis marker of localized PCa(a) CD44 expression in low-, medium-, and high-risk of human PCa was analyzed in IHC staining. (b &c) The expression levels of CD44 in 118 PCa patient samples were analyzed. A cut-off value of 10% was determined from the receiver operating characteristic (ROC) curve. Low and high CD44 staining were related to the disease risk but not age. (d & e) Kaplan-Meier curve analyzed the relationship between expression level of CD44 and biochemical recurrence or distant metastasis. Significance was defined as p<0.05(*) (f) Summarize the mechanism of ADT enhanced prostate cancer metastasis via alternation the TGFβ1-CD44 signaling.
Mentions: Due to CD44+ cell population increased was one of essential conditions for EMT in CRPC, we further detected whether expression of CD44 was correlated with prognosis in clinic. The expression of CD44 was analyzed in 118 PCa patient samples. A cut-off value of 10% was determined from the receiver operating characteristic (ROC) curve, and according to this value, two groups (low and high CD44 staining) were assigned. The high level expression of CD44 was significantly related to the disease risk but not in age subgroup (Fig.7a-c). Kaplan-Meier curve was addressed to evaluate the role of CD44 as a prognosis marker, showing that high expression level of CD44 was associated with biochemical recurrence and distant metastasis (Fig.7d&7e). The above clinical data suggested that CD44 may become a poor prognosis marker of PCa.

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