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Human Ly‐6 antigen E48 (Ly‐6D) regulates important interaction parameters between endothelial cells and head‐and‐neck squamous carcinoma cells
Author(s) -
Eshel Rinat,
Zanin Alexandra,
Kapon Dina,
SagiAssif Orit,
Brakenhoff Ruud,
van Dongen Guus,
Witz Isaac P.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10301
Subject(s) - head and neck squamous cell carcinoma , chemotaxis , transfection , biology , angiogenesis , cancer research , microbiology and biotechnology , chemistry , cell culture , cancer , biochemistry , receptor , head and neck cancer , genetics
Abstract Selectin ligands are crucial components in the interaction between endothelial cells and extravasating cancer cells and, thus, play an important role in metastasis formation. Head‐and‐neck squamous cell carcinoma (HNSCC) variants expressing high levels of E48, a human Ly‐6 protein (E48 hi ), expressed higher levels of the fucose‐generating FX enzyme and of the fucosylated E‐selectin ligand sLe a than cells expressing low levels of E48 (E48 lo ). Signaling through E48 upregulated expression levels of these molecules in HNSCC. In this work, we provide further evidence supporting the E48–FX–sLe a link by showing that FX antisense oligonucleotides reduced sLe a expression levels in HNSCC. We also show that E48 may be causally involved in regulating expression levels in HNSCC of 2 additional enzymes involved in the biosynthesis of sLe a , namely, ST‐30 and FucTIII. Also, selectin‐mediated adhesion of E48 hi variants to activated HUVECs was significantly higher than that of E48 lo variants. Transfection experiments utilizing sense or antisense E48 cDNA indicated that E48 may be causally involved in this adhesion. Chemokines are involved in the extravasation process of tumor cells. The release of chemoattractants from HNSCC variants differing in E48 expression was therefore analyzed. HNSCC did not release any chemoattractants but induced the release of such factors from HUVECs. Supernatants from E48 hi variants were significantly more efficient than E48 lo cells at inducing the release of chemoattractants from HUVECs. Transfection experiments indicated that E48 may be causally involved in the induction of chemoattractant release from HUVECs. Angiogenesis is an important manifestation of cancer–endothelium interactions. We therefore assayed for the presence of angiogenic factors in culture supernatants of HNSCC. Supernatants from E48 lo variants contained significantly higher amounts of PDGF than E48 hi cells. Transfection experiments indicated that E48 may be causally involved. Taken together, our results suggest that E48 controls important interaction parameters between HNSCC and endothelial cells. © 2002 Wiley‐Liss, Inc.