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Development of a therapy against metastatic bladder cancer using an interleukin-2 surface-modified MB49 bladder cancer stem cells vaccine.

Zhu YT, Pang SY, Lei CY, Luo Y, Chu QJ, Tan WL - Stem Cell Res Ther (2015)

Bottom Line: Accordingly, we developed a SA-IL-2-modified MCSCs vaccine and evaluated its antitumor effects.MCSCs had higher level of CD133 and CD44, less susceptibility to chemotherapy, more pronounced migration and greater tumorigenic ability.The SA-IL-2 MCSCs vaccine induced an antitumor immune response and was used to eliminate MCSCs to prevent tumor regrowth.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China. zhuyongtong@sina.com.

ABSTRACT

Introduction: In previous study the streptavidin interleukin-2 (SA-IL-2)-modified MB49 vaccine was effective against bladder cancer in a mouse model. However, a small portion of tumors regrew because the vaccine could not eliminate MB49 bladder cancer stem cells (MCSCs). Accordingly, we developed a SA-IL-2-modified MCSCs vaccine and evaluated its antitumor effects.

Methods: MCSCs were isolated and identified in cancer stem cells (CSCs) characters, with high expression of CSCs markers, higher resistance to chemotherapy, greater migration in vitro, and stronger tumorigenicity in vivo. The SA-IL-2 MCSCs vaccine was prepared and its bioactivity was evaluated. The protective, therapeutic, specific and memory immune response in animal experiments were designed to identify whether the vaccine elicited antitumor immunity and acted against metastatic bladder cancer.

Results: MCSCs had higher level of CD133 and CD44, less susceptibility to chemotherapy, more pronounced migration and greater tumorigenic ability. The successfully prepared SA-IL-2 MCSCs vaccine inhibited the tumor volume and prolonged mice survival in animal experiments. The expression of IgG, the population of dendritic cells, CD8(+) and CD4(+) T cells were highest in the experimental group than in the four control groups.

Conclusions: The SA-IL-2 MCSCs vaccine induced an antitumor immune response and was used to eliminate MCSCs to prevent tumor regrowth.

No MeSH data available.


Related in: MedlinePlus

Identification of MCSCs in CSCs characters. a FCM analysis showed that the fraction of CD44+CD133+ cells in the MCSCs population was larger than in MB49 cells. b WB analysis showed that CD133 and CD44 were abundantly expressed in MCSCs but poorly expressed in MB49 cells. β-actin was used as a protein loading control. c qPCR analysis revealed that the relative levels of CD133 and CD44 mRNA in MCSCs were higher in MB49 cells. d MCSCs exhibited higher cell viabilities after being exposed to different concentrations of paclitaxel and cisplatin. e In the transwell migration assay, the number of invasive MCSCs was higher than that of MB49 cells. f In xenograft formation experiments, MCSCs produced larger tumor volumes than MB49 cells did. *P < 0.05 (vs MB49 cells). MCSCs MB49 bladder cancer stem cells, CSCs cancer stem cells, FCM flow cytometry, WB Western blot, qPCR quantitative polymerase chain reaction
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Fig1: Identification of MCSCs in CSCs characters. a FCM analysis showed that the fraction of CD44+CD133+ cells in the MCSCs population was larger than in MB49 cells. b WB analysis showed that CD133 and CD44 were abundantly expressed in MCSCs but poorly expressed in MB49 cells. β-actin was used as a protein loading control. c qPCR analysis revealed that the relative levels of CD133 and CD44 mRNA in MCSCs were higher in MB49 cells. d MCSCs exhibited higher cell viabilities after being exposed to different concentrations of paclitaxel and cisplatin. e In the transwell migration assay, the number of invasive MCSCs was higher than that of MB49 cells. f In xenograft formation experiments, MCSCs produced larger tumor volumes than MB49 cells did. *P < 0.05 (vs MB49 cells). MCSCs MB49 bladder cancer stem cells, CSCs cancer stem cells, FCM flow cytometry, WB Western blot, qPCR quantitative polymerase chain reaction

Mentions: Flow cytometry (FCM) analysis revealed that the fraction of CD44+CD133+ cells was 25.97±1.31 % in MCSCs and 12.70±0.66 % in MB49 cells (Fig. 1a). The WB analysis indicated that the CD133 and CD44 proteins were abundantly expressed in MCSCs, but much less in MB49 cells (Fig. 1b). The qPCR analysis showed that the relative levels of CD133 and CD44 mRNAs in MCSCs were 2.7 and 4.7 times higher, respectively, than those observed in MB49 cells (Fig. 1c).Fig. 1


Development of a therapy against metastatic bladder cancer using an interleukin-2 surface-modified MB49 bladder cancer stem cells vaccine.

Zhu YT, Pang SY, Lei CY, Luo Y, Chu QJ, Tan WL - Stem Cell Res Ther (2015)

Identification of MCSCs in CSCs characters. a FCM analysis showed that the fraction of CD44+CD133+ cells in the MCSCs population was larger than in MB49 cells. b WB analysis showed that CD133 and CD44 were abundantly expressed in MCSCs but poorly expressed in MB49 cells. β-actin was used as a protein loading control. c qPCR analysis revealed that the relative levels of CD133 and CD44 mRNA in MCSCs were higher in MB49 cells. d MCSCs exhibited higher cell viabilities after being exposed to different concentrations of paclitaxel and cisplatin. e In the transwell migration assay, the number of invasive MCSCs was higher than that of MB49 cells. f In xenograft formation experiments, MCSCs produced larger tumor volumes than MB49 cells did. *P < 0.05 (vs MB49 cells). MCSCs MB49 bladder cancer stem cells, CSCs cancer stem cells, FCM flow cytometry, WB Western blot, qPCR quantitative polymerase chain reaction
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4644293&req=5

Fig1: Identification of MCSCs in CSCs characters. a FCM analysis showed that the fraction of CD44+CD133+ cells in the MCSCs population was larger than in MB49 cells. b WB analysis showed that CD133 and CD44 were abundantly expressed in MCSCs but poorly expressed in MB49 cells. β-actin was used as a protein loading control. c qPCR analysis revealed that the relative levels of CD133 and CD44 mRNA in MCSCs were higher in MB49 cells. d MCSCs exhibited higher cell viabilities after being exposed to different concentrations of paclitaxel and cisplatin. e In the transwell migration assay, the number of invasive MCSCs was higher than that of MB49 cells. f In xenograft formation experiments, MCSCs produced larger tumor volumes than MB49 cells did. *P < 0.05 (vs MB49 cells). MCSCs MB49 bladder cancer stem cells, CSCs cancer stem cells, FCM flow cytometry, WB Western blot, qPCR quantitative polymerase chain reaction
Mentions: Flow cytometry (FCM) analysis revealed that the fraction of CD44+CD133+ cells was 25.97±1.31 % in MCSCs and 12.70±0.66 % in MB49 cells (Fig. 1a). The WB analysis indicated that the CD133 and CD44 proteins were abundantly expressed in MCSCs, but much less in MB49 cells (Fig. 1b). The qPCR analysis showed that the relative levels of CD133 and CD44 mRNAs in MCSCs were 2.7 and 4.7 times higher, respectively, than those observed in MB49 cells (Fig. 1c).Fig. 1

Bottom Line: Accordingly, we developed a SA-IL-2-modified MCSCs vaccine and evaluated its antitumor effects.MCSCs had higher level of CD133 and CD44, less susceptibility to chemotherapy, more pronounced migration and greater tumorigenic ability.The SA-IL-2 MCSCs vaccine induced an antitumor immune response and was used to eliminate MCSCs to prevent tumor regrowth.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China. zhuyongtong@sina.com.

ABSTRACT

Introduction: In previous study the streptavidin interleukin-2 (SA-IL-2)-modified MB49 vaccine was effective against bladder cancer in a mouse model. However, a small portion of tumors regrew because the vaccine could not eliminate MB49 bladder cancer stem cells (MCSCs). Accordingly, we developed a SA-IL-2-modified MCSCs vaccine and evaluated its antitumor effects.

Methods: MCSCs were isolated and identified in cancer stem cells (CSCs) characters, with high expression of CSCs markers, higher resistance to chemotherapy, greater migration in vitro, and stronger tumorigenicity in vivo. The SA-IL-2 MCSCs vaccine was prepared and its bioactivity was evaluated. The protective, therapeutic, specific and memory immune response in animal experiments were designed to identify whether the vaccine elicited antitumor immunity and acted against metastatic bladder cancer.

Results: MCSCs had higher level of CD133 and CD44, less susceptibility to chemotherapy, more pronounced migration and greater tumorigenic ability. The successfully prepared SA-IL-2 MCSCs vaccine inhibited the tumor volume and prolonged mice survival in animal experiments. The expression of IgG, the population of dendritic cells, CD8(+) and CD4(+) T cells were highest in the experimental group than in the four control groups.

Conclusions: The SA-IL-2 MCSCs vaccine induced an antitumor immune response and was used to eliminate MCSCs to prevent tumor regrowth.

No MeSH data available.


Related in: MedlinePlus