Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines.

Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print Cited Medium: Print ISSN: 0007-0920 (Print) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE

Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.

Antineoplastic Agents/*adverse effects ; Carcinoma, Squamous Cell/*pathology ; Isotretinoin/*adverse effects ; Mouth Neoplasms/*pathology ; Tretinoin/*adverse effects; Carcinoma, Squamous Cell/enzymology ; Carcinoma, Squamous Cell/metabolism ; Cell Division/drug effects ; Collagenases/metabolism ; Dose-Response Relationship, Drug ; Enzyme Activation ; Enzyme Precursors/metabolism ; Gelatinases/metabolism ; Humans ; Matrix Metalloproteinase 9 ; Matrix Metalloproteinases, Membrane-Associated ; Metalloendopeptidases/biosynthesis ; Metalloendopeptidases/metabolism ; Mouth Neoplasms/enzymology ; Mouth Neoplasms/metabolism ; Neoplasm Invasiveness ; Receptors, Retinoic Acid/biosynthesis ; Tissue Inhibitor of Metalloproteinase-1/biosynthesis ; Tissue Inhibitor of Metalloproteinase-2/biosynthesis ; Tissue Plasminogen Activator/biosynthesis ; Tumor Cells, Cultured/drug effects ; Urokinase-Type Plasminogen Activator/biosynthesis

Retinoids inhibit the proliferation of several types of tumour cells, and are used for patients with several malignant tumours. In this study, we examined the effect of retinoic acids (RAs) on the invasive potentials of the oral squamous cell carcinoma (SCC) cells, BHY and HNt. BHY cells expressed all of retinoid nuclear receptors (RARalpha, beta, gamma, and RXRalpha) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2). HNt cells lacked the expression of RARbeta, but expressed other nuclear receptors and CRABPs. All-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-cisRA) (10(-6)and 10(-7)M) inhibited the growth of the cells, but low-dose ATRA and 13-cisRA (10(-8)M) marginally affected the growth of the cells. Surprisingly, low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9). Activation of proMMP2 and proMMP9 was inhibited by aprotinin, a serine-proteinase, tPA inhibitor. Furthermore, low-dose RAs enhanced the in vitro invasiveness of BHY cells. These results indicate that low-dose RAs enhances the in vitro invasiveness of oral SCC cells via an activation of proMMP2 and proMMP9 probably mediated by the induction of tPA.
(Copyright 2001 Cancer Research Campaign.)

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0 (Antineoplastic Agents)
0 (Enzyme Precursors)
0 (Receptors, Retinoic Acid)
0 (Tissue Inhibitor of Metalloproteinase-1)
0 (retinoic acid binding protein I, cellular)
0 (retinoic acid binding protein II, cellular)
127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
5688UTC01R (Tretinoin)
EC 3.4.21.68 (Tissue Plasminogen Activator)
EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
EC 3.4.24.- (Collagenases)
EC 3.4.24.- (Gelatinases)
EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
EC 3.4.24.- (Metalloendopeptidases)
EC 3.4.24.- (pro-matrix metalloproteinase 9)
EC 3.4.24.- (progelatinase)
EC 3.4.24.35 (Matrix Metalloproteinase 9)
EH28UP18IF (Isotretinoin)

Date Created: 20010705 Date Completed: 20010809 Latest Revision: 20181113

20250114

PMC2363904

10.1054/bjoc.2001.1862

11437413