Overexpression of CXC-chemokines and CXC-chemokine receptor type II constitute an autocrine growth mechanism in the epidermoid carcinoma cells KB and A431.
The CXC-chemokines Groalpha and interleukin-8 (IL-8) are well characterized growth factors for melanoma cells. Here the constitutive expression of Groalpha, IL-8 and their receptors (CXCR1 and CXCR2) as well as their functional involvement in the proliferation response were analyzed in normal keratinocytes and epidermoid carcinoma cell lines A431 and KB. Flow cytometric measurements, ELISA and semi-quantitative RT-PCR revealed low constitutive protein secretion and mRNA expression of both CXC-chemokines as well as CXCR1 and 2 in normal keratinocytes, whereas significant higher levels of CXC-chemokines and CXCR2 were deteced in epidermoid carcinoma cells. Proliferation of epidermoid carcinoma cells could be induced by CXC-chemokines and constitutive proliferation could be inhibited by neutralizing antibodies against CXC-chemokines and CXCR2. These studies indicate that constitutive Groalpha, IL-8 and CXCR2 protein expression enable an autocrine growth mechanism in epidermoid carcinoma cells.
Metzner
B
B
Clinic of Dermatology, Divisions of Experimental and Clinical Dermatology, University of Freiburg, Freiburg, Germany.
Hofmann
C
C
Heinemann
C
C
Zimpfer
U
U
Schraufstätter
I
I
Schöpf
E
E
Norgauer
J
J
D015703:Antigens, CD / Q000096:biosynthesis*; D019898:Autocrine Communication; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis; D002630:Chemotactic Factors / Q000096:biosynthesis*; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B