Enhanced angiogenesis due to inflammatory cytokines from pancreatic cancer cell lines and relation to metastatic potential.
OBJECTIVE
To investigate the mechanisms of metastasis formation in human pancreatic carcinoma, we examined the angiogenic capabilities of human pancreatic cancer cell lines with different metastatic potentials and the roles of inflammatory cytokines.


METHODS
Interleukin (IL)-8 secretion by human pancreatic cancer cells stimulated with IL-1alpha or IL-1 receptor antagonist (IL-1ra) was measured by enzyme-linked immunosorbent assay (ELISA). We then examined how cancer cells with different metastatic potentials influenced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method (MTT assay) and an angiogenesis assay, respectively. We also examined the role of inflammatory cytokines in relation to tumor metastatic potential and angiogenesis.


RESULTS
IL-8 secretion levels by pancreatic cancer cells were regulated by IL-1alpha and correlated with metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with metastatic pancreatic cancer cells and were enhanced to a similar extent by culture in the presence of IL-1alpha and IL-8. In contrast, blockade of IL-1alpha or IL-8 inhibited HUVEC proliferation and angiogenesis.


CONCLUSIONS
The inflammatory cytokines IL-1alpha and IL-8 may have an important role in metastasis via vascular endothelial cell proliferation and angiogenesis.
Matsuo
Yoichi
Y
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. matsuo@med.nagoya-cu.ac.jp
Sawai
Hirozumi
H
Funahashi
Hitoshi
H
Takahashi
Hiroki
H
Sakamoto
Masaki
M
Yamamoto
Minoru
M
Okada
Yuji
Y
Hayakawa
Tetsushi
T
Manabe
Tadao
T
D002455:Cell Division; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000494:pharmacology; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger