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P-selectin-mediated platelet adhesion promotes tumor growth.

Qi C, Wei B, Zhou W, Yang Y, Li B, Guo S, Li J, Ye J, Li J, Zhang Q, Lan T, He X, Cao L, Zhou J, Geng J, Wang L - Oncotarget (2015)

Bottom Line: P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth.Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail.Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.

ABSTRACT
Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.

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Soluble P-selectin inhibits tumor growth and abolishes platelet recruitment in Rip1-Tag2 mice and xenografted human colorectal cancer(A and B) Effects of mP-sel-Fc on insulinoma growth and angiogenesis in Rip1-Tag2 mice. Following intravenous administration of mIgG or mP-sel-Fc through the tail veins of Rip-Tag2 mice, tumor volume (A) and angiogenic islet number (B) were assessed. (C) mP-sel-Fc did not affect the bleeding time of Rip1-Tag2 mice. (D) Imunofluorescent images of GFP-expressing platelets, T-antigen-positive tumor cells (yellow), CD31-positive endothelial cells (red) and DAPI-positive cell nuclei (blue) in pancreas islet insulinomas were examined and showed that mP-sel-Fc abolished the infiltration of platelets into insulinoma. (E and F) The colorectal cancer-bearing mice were treated intravenously with hIgG or hP-sel-Fc. The tumor volume and weigh were calculated. (G) The effect of hP-sel-Fc on bleeding time of mice. (H) The accumulation of platelets in xenografted colorectal cancer significantly decreased. *p < 0.05; **p < 0.01. Bar = 20 μm.
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Figure 3: Soluble P-selectin inhibits tumor growth and abolishes platelet recruitment in Rip1-Tag2 mice and xenografted human colorectal cancer(A and B) Effects of mP-sel-Fc on insulinoma growth and angiogenesis in Rip1-Tag2 mice. Following intravenous administration of mIgG or mP-sel-Fc through the tail veins of Rip-Tag2 mice, tumor volume (A) and angiogenic islet number (B) were assessed. (C) mP-sel-Fc did not affect the bleeding time of Rip1-Tag2 mice. (D) Imunofluorescent images of GFP-expressing platelets, T-antigen-positive tumor cells (yellow), CD31-positive endothelial cells (red) and DAPI-positive cell nuclei (blue) in pancreas islet insulinomas were examined and showed that mP-sel-Fc abolished the infiltration of platelets into insulinoma. (E and F) The colorectal cancer-bearing mice were treated intravenously with hIgG or hP-sel-Fc. The tumor volume and weigh were calculated. (G) The effect of hP-sel-Fc on bleeding time of mice. (H) The accumulation of platelets in xenografted colorectal cancer significantly decreased. *p < 0.05; **p < 0.01. Bar = 20 μm.

Mentions: Because P-selectin-mediated platelet accumulation accelerates insulinoma growth, we recombined mP-sel-Fc and hP-sel-Fc [22] to treat the 5-weeks-old or 9 weeks-old Rip1-Tag2 mice for three weeks and xenografted human colorectal cancers. We found that the intravenous administration of mP-sel-Fc, but not mouse IgG, suppressed angiogenic islets in 8-weeks-old Rip1-Tag2 mice and volume in 12-weeks-old Rip1-Tag2 mice (Figures 3A and 3B), but did not inhibit the angiogenic islets in 12-weeks-old Rip1-Tag2 mice (Figure 3A). At 5–8 weeks, 4 Rip1-Tag2 mice (n = 11) bore insulinomas following mIgG treatment while none of them (n = 8) had any insulinomas following mP-sel-Fc treatment (data not shown). Furthermore, the mP-sel-Fc abolished platelet adhesion in the insulinomas of Rip1-Tag2 mice (Figure 3D).


P-selectin-mediated platelet adhesion promotes tumor growth.

Qi C, Wei B, Zhou W, Yang Y, Li B, Guo S, Li J, Ye J, Li J, Zhang Q, Lan T, He X, Cao L, Zhou J, Geng J, Wang L - Oncotarget (2015)

Soluble P-selectin inhibits tumor growth and abolishes platelet recruitment in Rip1-Tag2 mice and xenografted human colorectal cancer(A and B) Effects of mP-sel-Fc on insulinoma growth and angiogenesis in Rip1-Tag2 mice. Following intravenous administration of mIgG or mP-sel-Fc through the tail veins of Rip-Tag2 mice, tumor volume (A) and angiogenic islet number (B) were assessed. (C) mP-sel-Fc did not affect the bleeding time of Rip1-Tag2 mice. (D) Imunofluorescent images of GFP-expressing platelets, T-antigen-positive tumor cells (yellow), CD31-positive endothelial cells (red) and DAPI-positive cell nuclei (blue) in pancreas islet insulinomas were examined and showed that mP-sel-Fc abolished the infiltration of platelets into insulinoma. (E and F) The colorectal cancer-bearing mice were treated intravenously with hIgG or hP-sel-Fc. The tumor volume and weigh were calculated. (G) The effect of hP-sel-Fc on bleeding time of mice. (H) The accumulation of platelets in xenografted colorectal cancer significantly decreased. *p < 0.05; **p < 0.01. Bar = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466636&req=5

Figure 3: Soluble P-selectin inhibits tumor growth and abolishes platelet recruitment in Rip1-Tag2 mice and xenografted human colorectal cancer(A and B) Effects of mP-sel-Fc on insulinoma growth and angiogenesis in Rip1-Tag2 mice. Following intravenous administration of mIgG or mP-sel-Fc through the tail veins of Rip-Tag2 mice, tumor volume (A) and angiogenic islet number (B) were assessed. (C) mP-sel-Fc did not affect the bleeding time of Rip1-Tag2 mice. (D) Imunofluorescent images of GFP-expressing platelets, T-antigen-positive tumor cells (yellow), CD31-positive endothelial cells (red) and DAPI-positive cell nuclei (blue) in pancreas islet insulinomas were examined and showed that mP-sel-Fc abolished the infiltration of platelets into insulinoma. (E and F) The colorectal cancer-bearing mice were treated intravenously with hIgG or hP-sel-Fc. The tumor volume and weigh were calculated. (G) The effect of hP-sel-Fc on bleeding time of mice. (H) The accumulation of platelets in xenografted colorectal cancer significantly decreased. *p < 0.05; **p < 0.01. Bar = 20 μm.
Mentions: Because P-selectin-mediated platelet accumulation accelerates insulinoma growth, we recombined mP-sel-Fc and hP-sel-Fc [22] to treat the 5-weeks-old or 9 weeks-old Rip1-Tag2 mice for three weeks and xenografted human colorectal cancers. We found that the intravenous administration of mP-sel-Fc, but not mouse IgG, suppressed angiogenic islets in 8-weeks-old Rip1-Tag2 mice and volume in 12-weeks-old Rip1-Tag2 mice (Figures 3A and 3B), but did not inhibit the angiogenic islets in 12-weeks-old Rip1-Tag2 mice (Figure 3A). At 5–8 weeks, 4 Rip1-Tag2 mice (n = 11) bore insulinomas following mIgG treatment while none of them (n = 8) had any insulinomas following mP-sel-Fc treatment (data not shown). Furthermore, the mP-sel-Fc abolished platelet adhesion in the insulinomas of Rip1-Tag2 mice (Figure 3D).

Bottom Line: P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth.Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail.Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.

ABSTRACT
Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.

Show MeSH
Related in: MedlinePlus