Interleukin-8 inhibits non-small cell lung cancer proliferation: a possible role for regulation of tumor growth by autocrine and paracrine pathways.
Interleukin-8 (IL-8) is an 8 kD chemokine and angiogenic factor produced by alveolar macrophages, endothelial cells, monocytes, fibroblasts, T lymphocytes, and epithelial cells in response to a variety of stimuli, including LPS, TNF-alpha, IL-1, IL-7, and hypoxia. Pulmonary tumors produce a variety of growth factors and cytokines that may act in both autocrine and paracrine fashion. A549, a well-characterized human lung adenocarcinoma line, was cloned for different levels of IL-8 production by limiting dilution. Clone 3B4 produced 361 +/- 73 pg/ml, and clone 2B2 produced 7818 +/- 614 pg/ml of IL-8 (p = 0.003). Clone 3B4 proliferated at 1.7 times the rate of 2B2. Anti-IL-8 reversed the decrement in proliferation of clone 2B2 by 50%, but recombinant IL-8 decreased the proliferation of 3B4 by 40-55% compared with control. In addition to A549, three other non-small cell lung cancer (NSCLC) lines showed significantly decreased proliferation in response to exogenous recombinant IL-8 (5-30 ng/ml; p < 0.05). These findings suggest that in addition to its chemotactic and angiogenic activities, IL-8 may inhibit lung tumor proliferation by both autocrine and paracrine pathways.
Wang
J
J
Pulmonary Immunology Laboratory, University of California-Los Angeles School of Medicine, USA.
Huang
M
M
Lee
P
P
Komanduri
K
K
Sharma
S
S
Chen
G
G
Dubinett
S M
SM
D015703:Antigens, CD / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D006728:Hormones / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000032:analysis; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000970:Antineoplastic Agents; D006728:Hormones; D016209:Interleukin-8; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins