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Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.

Horiguchi H, Endo M, Miyamoto Y, Sakamoto Y, Odagiri H, Masuda T, Kadomatsu T, Tanoue H, Motokawa I, Terada K, Morioka MS, Manabe I, Baba H, Oike Y - Cancer Sci. (2014)

Bottom Line: Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells.Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells.To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

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Higher angiopoietin-like protein 2 (ANGPTL2) expression in primary tumor tissues from colorectal cancer patients correlates with a lower objective response rate. ANGPTL2 immunostaining in primary tumors from CRC patients. (a) Representative images of ANGPTL2 low (<50% ANGPTL2-positive tumor cells; left) and ANGPTL2-high (≥50% ANGPTL2-positive tumor cells; right) specimens. Scale bar = 100 μm. (b) Summary of overall responses to chemotherapy and ANGPTL2 expression in CRC patient specimens. P < 0.05 (Fisher's exact test).
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fig06: Higher angiopoietin-like protein 2 (ANGPTL2) expression in primary tumor tissues from colorectal cancer patients correlates with a lower objective response rate. ANGPTL2 immunostaining in primary tumors from CRC patients. (a) Representative images of ANGPTL2 low (<50% ANGPTL2-positive tumor cells; left) and ANGPTL2-high (≥50% ANGPTL2-positive tumor cells; right) specimens. Scale bar = 100 μm. (b) Summary of overall responses to chemotherapy and ANGPTL2 expression in CRC patient specimens. P < 0.05 (Fisher's exact test).

Mentions: We next carried out ANGPTL2 immunostaining using tissues from 92 CRC patients with unresectable tumors in order to correlate ANGPTL2 expression with the ORR to chemotherapy (Fig. 6, Table S2). Patients were placed into high- and low-ANGPTL2 groups: the high group showed ≥50% of ANGPTL2-positive tumor cells and the low showed <50% (Fig. 6a). The percentage of patients who showed a response to chemotherapy was significantly lower in the high-ANGPTL2 than the low-ANGPTL2 group (Fig. 6b, P < 0.05), although progression-free survival and overall survival did not differ significantly between groups (data not shown). This analysis suggests that high ANGPTL2 expression in CRC cells is associated with chemoresistance.


Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.

Horiguchi H, Endo M, Miyamoto Y, Sakamoto Y, Odagiri H, Masuda T, Kadomatsu T, Tanoue H, Motokawa I, Terada K, Morioka MS, Manabe I, Baba H, Oike Y - Cancer Sci. (2014)

Higher angiopoietin-like protein 2 (ANGPTL2) expression in primary tumor tissues from colorectal cancer patients correlates with a lower objective response rate. ANGPTL2 immunostaining in primary tumors from CRC patients. (a) Representative images of ANGPTL2 low (<50% ANGPTL2-positive tumor cells; left) and ANGPTL2-high (≥50% ANGPTL2-positive tumor cells; right) specimens. Scale bar = 100 μm. (b) Summary of overall responses to chemotherapy and ANGPTL2 expression in CRC patient specimens. P < 0.05 (Fisher's exact test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317964&req=5

fig06: Higher angiopoietin-like protein 2 (ANGPTL2) expression in primary tumor tissues from colorectal cancer patients correlates with a lower objective response rate. ANGPTL2 immunostaining in primary tumors from CRC patients. (a) Representative images of ANGPTL2 low (<50% ANGPTL2-positive tumor cells; left) and ANGPTL2-high (≥50% ANGPTL2-positive tumor cells; right) specimens. Scale bar = 100 μm. (b) Summary of overall responses to chemotherapy and ANGPTL2 expression in CRC patient specimens. P < 0.05 (Fisher's exact test).
Mentions: We next carried out ANGPTL2 immunostaining using tissues from 92 CRC patients with unresectable tumors in order to correlate ANGPTL2 expression with the ORR to chemotherapy (Fig. 6, Table S2). Patients were placed into high- and low-ANGPTL2 groups: the high group showed ≥50% of ANGPTL2-positive tumor cells and the low showed <50% (Fig. 6a). The percentage of patients who showed a response to chemotherapy was significantly lower in the high-ANGPTL2 than the low-ANGPTL2 group (Fig. 6b, P < 0.05), although progression-free survival and overall survival did not differ significantly between groups (data not shown). This analysis suggests that high ANGPTL2 expression in CRC cells is associated with chemoresistance.

Bottom Line: Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells.Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells.To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Show MeSH
Related in: MedlinePlus