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Higher proliferation of peritumoral endothelial cells to IL-6/sIL-6R than tumoral endothelial cells in hepatocellular carcinoma.

Zhuang PY, Wang JD, Tang ZH, Zhou XP, Quan ZW, Liu YB, Shen J - BMC Cancer (2015)

Bottom Line: Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth.The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT.PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kong jiang Street, Shanghai, 200082, China. pyzhuang@gmail.com.

ABSTRACT

Background: This study aimed to explore the responses to the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex in peritumoral endothelial cells (PECs) and tumor endothelial cells (TECs), as well as determine the signaling pathways in the angiogenesis of hepatocellular carcinoma (HCC).

Methods: The expression of IL-6, IL-6R, gp130, CD68, HIF-1α, and microvessel density (MVD) were assessed with an orthotopic xenograft model in nude mice. ECs were incubated under hypoxic conditions to detect IL-6 and gp130. The proliferation of PECs and TECs in the presence of IL-6 and sIL-6R, as well as the expression of gp130, JAK2/STAT3, PI3K/AKT in endothelial cells were measured.

Results: Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth. Hypoxia could directly induce IL-6 expression, but not gp130 in PECs. The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT.

Conclusions: PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3. PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment.

No MeSH data available.


Related in: MedlinePlus

a–d Effect of IL-6 and sIL-6R on the proliferation of PECs and TECs. IL-6 or sIL-6R alone had no effect on the proliferation on PECs and TECs. The co-culture of both IL-6 and sIL-6R could induce PEC and TEC proliferation. PECs showed much higher proliferation in response to the co-cultured environment for 48 and 72 h as compared with TECs. Representative images of PECs (a) and TECs (b) in different culture conditions after 48 h. Absorbance of PECs (c) and TECs (d) at 24, 48, and 72 h in different culture conditionss
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Fig3: a–d Effect of IL-6 and sIL-6R on the proliferation of PECs and TECs. IL-6 or sIL-6R alone had no effect on the proliferation on PECs and TECs. The co-culture of both IL-6 and sIL-6R could induce PEC and TEC proliferation. PECs showed much higher proliferation in response to the co-cultured environment for 48 and 72 h as compared with TECs. Representative images of PECs (a) and TECs (b) in different culture conditions after 48 h. Absorbance of PECs (c) and TECs (d) at 24, 48, and 72 h in different culture conditionss

Mentions: We subsequently determined the effects of IL-6 and sIL-6R on EC proliferation, and found that neither IL-6 nor sIL-6R alone had an effect on the proliferation of PECs and TECs (Fig. 3). To determine whether the presence of both IL-6 and sIL-6R can induce the proliferation of PECs and TECs, we co-cultured both cell types with IL-6 and sIL-6R. Interestingly, the proliferation of both PECs and TECs was much higher when the cells were grown together with IL-6 and sIL-6R compared with that of cells grown with either IL-6 or sIL-6R for 48 h and 72 h (especially predominant for 48 h), and no obvious different was observed in 24 h. Therefore, cell proliferation increased in response to the co-culture environment. Further, PECs showed a much higher rate of proliferation in response to the co-culture environment than TECs [2.65 ± 0.01 vs. 2.25 ± 0.02 for PECs under the co-cultured and vehicle conditions for 48 h, respectively (P = 0.0004); 1.50 ± 0.01 vs. 1.37 ± 0.01 for TECs under the co-cultured and vehicle conditions for 48 h, respectively (P = 0.029)]; cell proliferation was evaluated by the CCK-8 assay; Fig. 3, Table 1].Fig. 3


Higher proliferation of peritumoral endothelial cells to IL-6/sIL-6R than tumoral endothelial cells in hepatocellular carcinoma.

Zhuang PY, Wang JD, Tang ZH, Zhou XP, Quan ZW, Liu YB, Shen J - BMC Cancer (2015)

a–d Effect of IL-6 and sIL-6R on the proliferation of PECs and TECs. IL-6 or sIL-6R alone had no effect on the proliferation on PECs and TECs. The co-culture of both IL-6 and sIL-6R could induce PEC and TEC proliferation. PECs showed much higher proliferation in response to the co-cultured environment for 48 and 72 h as compared with TECs. Representative images of PECs (a) and TECs (b) in different culture conditions after 48 h. Absorbance of PECs (c) and TECs (d) at 24, 48, and 72 h in different culture conditionss
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4629315&req=5

Fig3: a–d Effect of IL-6 and sIL-6R on the proliferation of PECs and TECs. IL-6 or sIL-6R alone had no effect on the proliferation on PECs and TECs. The co-culture of both IL-6 and sIL-6R could induce PEC and TEC proliferation. PECs showed much higher proliferation in response to the co-cultured environment for 48 and 72 h as compared with TECs. Representative images of PECs (a) and TECs (b) in different culture conditions after 48 h. Absorbance of PECs (c) and TECs (d) at 24, 48, and 72 h in different culture conditionss
Mentions: We subsequently determined the effects of IL-6 and sIL-6R on EC proliferation, and found that neither IL-6 nor sIL-6R alone had an effect on the proliferation of PECs and TECs (Fig. 3). To determine whether the presence of both IL-6 and sIL-6R can induce the proliferation of PECs and TECs, we co-cultured both cell types with IL-6 and sIL-6R. Interestingly, the proliferation of both PECs and TECs was much higher when the cells were grown together with IL-6 and sIL-6R compared with that of cells grown with either IL-6 or sIL-6R for 48 h and 72 h (especially predominant for 48 h), and no obvious different was observed in 24 h. Therefore, cell proliferation increased in response to the co-culture environment. Further, PECs showed a much higher rate of proliferation in response to the co-culture environment than TECs [2.65 ± 0.01 vs. 2.25 ± 0.02 for PECs under the co-cultured and vehicle conditions for 48 h, respectively (P = 0.0004); 1.50 ± 0.01 vs. 1.37 ± 0.01 for TECs under the co-cultured and vehicle conditions for 48 h, respectively (P = 0.029)]; cell proliferation was evaluated by the CCK-8 assay; Fig. 3, Table 1].Fig. 3

Bottom Line: Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth.The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT.PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kong jiang Street, Shanghai, 200082, China. pyzhuang@gmail.com.

ABSTRACT

Background: This study aimed to explore the responses to the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex in peritumoral endothelial cells (PECs) and tumor endothelial cells (TECs), as well as determine the signaling pathways in the angiogenesis of hepatocellular carcinoma (HCC).

Methods: The expression of IL-6, IL-6R, gp130, CD68, HIF-1α, and microvessel density (MVD) were assessed with an orthotopic xenograft model in nude mice. ECs were incubated under hypoxic conditions to detect IL-6 and gp130. The proliferation of PECs and TECs in the presence of IL-6 and sIL-6R, as well as the expression of gp130, JAK2/STAT3, PI3K/AKT in endothelial cells were measured.

Results: Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth. Hypoxia could directly induce IL-6 expression, but not gp130 in PECs. The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT.

Conclusions: PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3. PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment.

No MeSH data available.


Related in: MedlinePlus