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Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer.

Zhang Z, Wang M, Zhou L, Feng X, Cheng J, Yu Y, Gong Y, Zhu Y, Li C, Tian L, Huang Q - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: Interestedly, immunohistochemistry staining showed that positive HMGB1, CC3, and Ki67 expression were significantly higher in colorectal tumor tissues than in peritumoral tissues (p <0.01).The Kaplan-Meier survival analysis revealed that high HMGB1, CC3, and Ki67 levels were significantly associated with poor prognosis (p <0.05, p <0.01).Multivariate analysis using Cox proportional hazards model showed that TNM staging and HMGB1 were independent prognostic factors in patients with colorectal cancer (CRC) (p <0.01, p <0.001).

View Article: PubMed Central - PubMed

Affiliation: The Comprehensive Cancer Center & Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. kanardo@163.com.

ABSTRACT

Background: Dying tumor cells after irradiation could promote the proliferation of living tumor cells might cause tumor relapse and treatment failure. Our previous study showed that activated caspase-3 after irradiation probably participates in tumor repopulation. In this study, we investigated whether high mobility group box 1(HMGB1) is also involved in tumor repopulation.

Methods: Colorectal tumor cells were irradiated. The cleaved caspase-3 (CC3) in irradiated tumor cells and HMGB1 in the supernatant of irradiated tumor cells were detected by Western blot. A large number of irradiated colorectal tumor cells (feeder cells) were then co-cultured with a small number of luciferase-labeled living colorectal tumor cells (reporter cells) and proliferation of reporter cells was measured by bioluminescence imaging. The CC3 and HMGB1 protein expression in colorectal tumor and peritumoral tissues were detected by immunohistochemistry and their correlation with prognosis were analyzed.

Results: The irradiated colorectal tumor cells underwent apoptosis and necrosis and produced CC3 in tumor cells and HMGB1 in the supernatant of cultured cells. The increased expression of secretory HMGB1 correlated with CC3 level and proliferating cell nuclear antigen (PCNA) after irradiation in vitro. The irradiated dying cells remarkably stimulated living tumor cell proliferation. Interestedly, immunohistochemistry staining showed that positive HMGB1, CC3, and Ki67 expression were significantly higher in colorectal tumor tissues than in peritumoral tissues (p <0.01). The Kaplan-Meier survival analysis revealed that high HMGB1, CC3, and Ki67 levels were significantly associated with poor prognosis (p <0.05, p <0.01). Multivariate analysis using Cox proportional hazards model showed that TNM staging and HMGB1 were independent prognostic factors in patients with colorectal cancer (CRC) (p <0.01, p <0.001).

Conclusion: Both apoptotic and necrotic cells could stimulate proliferation of living tumor cells, and the increased expression of CC3 and HMGB1 in tumor cells could be new markers for poor prognosis in colorectal cancer patients.

No MeSH data available.


Related in: MedlinePlus

HMGB1, CC3, and Ki67 expression in colorectal cancer tissues in serial sectioning slides. (a, b and c) represented the positive immunohistochemical staining of HMGB1, CC3, and Ki67, respectively, while d, e and f represented the negative staining of the three proteins
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Fig3: HMGB1, CC3, and Ki67 expression in colorectal cancer tissues in serial sectioning slides. (a, b and c) represented the positive immunohistochemical staining of HMGB1, CC3, and Ki67, respectively, while d, e and f represented the negative staining of the three proteins

Mentions: Spearman’s rank correlation analysis further showed that HMGB1 positively correlated with CC3 and Ki67 level (correlation coefficient 0.5393, 0.3814, respectively; p <0.001, Table 5). Fig. 3 showed a coordinated expression of HMGB1, CC3, and Ki67 that they were either all positive or all negative/low expression in the same visual field.Table 5


Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer.

Zhang Z, Wang M, Zhou L, Feng X, Cheng J, Yu Y, Gong Y, Zhu Y, Li C, Tian L, Huang Q - J. Exp. Clin. Cancer Res. (2015)

HMGB1, CC3, and Ki67 expression in colorectal cancer tissues in serial sectioning slides. (a, b and c) represented the positive immunohistochemical staining of HMGB1, CC3, and Ki67, respectively, while d, e and f represented the negative staining of the three proteins
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4446854&req=5

Fig3: HMGB1, CC3, and Ki67 expression in colorectal cancer tissues in serial sectioning slides. (a, b and c) represented the positive immunohistochemical staining of HMGB1, CC3, and Ki67, respectively, while d, e and f represented the negative staining of the three proteins
Mentions: Spearman’s rank correlation analysis further showed that HMGB1 positively correlated with CC3 and Ki67 level (correlation coefficient 0.5393, 0.3814, respectively; p <0.001, Table 5). Fig. 3 showed a coordinated expression of HMGB1, CC3, and Ki67 that they were either all positive or all negative/low expression in the same visual field.Table 5

Bottom Line: Interestedly, immunohistochemistry staining showed that positive HMGB1, CC3, and Ki67 expression were significantly higher in colorectal tumor tissues than in peritumoral tissues (p <0.01).The Kaplan-Meier survival analysis revealed that high HMGB1, CC3, and Ki67 levels were significantly associated with poor prognosis (p <0.05, p <0.01).Multivariate analysis using Cox proportional hazards model showed that TNM staging and HMGB1 were independent prognostic factors in patients with colorectal cancer (CRC) (p <0.01, p <0.001).

View Article: PubMed Central - PubMed

Affiliation: The Comprehensive Cancer Center & Shanghai Key Laboratory for Pancreatic Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 201620, China. kanardo@163.com.

ABSTRACT

Background: Dying tumor cells after irradiation could promote the proliferation of living tumor cells might cause tumor relapse and treatment failure. Our previous study showed that activated caspase-3 after irradiation probably participates in tumor repopulation. In this study, we investigated whether high mobility group box 1(HMGB1) is also involved in tumor repopulation.

Methods: Colorectal tumor cells were irradiated. The cleaved caspase-3 (CC3) in irradiated tumor cells and HMGB1 in the supernatant of irradiated tumor cells were detected by Western blot. A large number of irradiated colorectal tumor cells (feeder cells) were then co-cultured with a small number of luciferase-labeled living colorectal tumor cells (reporter cells) and proliferation of reporter cells was measured by bioluminescence imaging. The CC3 and HMGB1 protein expression in colorectal tumor and peritumoral tissues were detected by immunohistochemistry and their correlation with prognosis were analyzed.

Results: The irradiated colorectal tumor cells underwent apoptosis and necrosis and produced CC3 in tumor cells and HMGB1 in the supernatant of cultured cells. The increased expression of secretory HMGB1 correlated with CC3 level and proliferating cell nuclear antigen (PCNA) after irradiation in vitro. The irradiated dying cells remarkably stimulated living tumor cell proliferation. Interestedly, immunohistochemistry staining showed that positive HMGB1, CC3, and Ki67 expression were significantly higher in colorectal tumor tissues than in peritumoral tissues (p <0.01). The Kaplan-Meier survival analysis revealed that high HMGB1, CC3, and Ki67 levels were significantly associated with poor prognosis (p <0.05, p <0.01). Multivariate analysis using Cox proportional hazards model showed that TNM staging and HMGB1 were independent prognostic factors in patients with colorectal cancer (CRC) (p <0.01, p <0.001).

Conclusion: Both apoptotic and necrotic cells could stimulate proliferation of living tumor cells, and the increased expression of CC3 and HMGB1 in tumor cells could be new markers for poor prognosis in colorectal cancer patients.

No MeSH data available.


Related in: MedlinePlus