Lingen M W, Polverini P J, Bouck N P
Department of Pathology, Northwestern University Medical and Dental Schools, Chicago, Illinois, USA.
Am J Pathol. 1996 Jul;149(1):247-58.
Retinoids have shown great promise as chemopreventive against the development of squamous cell carcinomas of the upper aerodigestive tract. However, the exact mechanism by which they block new tumors from arising is unknown. Here, we report that 13-cis- and all-trans-retinoic acid, used at clinically achievable doses of 10(-6) mol/L or less, can directly and specifically affect cell lines cultured from oral squamous cell carcinomas, inducing them to switch from an angiogenic to an anti-angiogenic phenotype. Although retinoic-acid-treated and untreated tumor cells make the same amount of interleukin-8, the major inducer of neovascularization produced by such tumor lines, they vary in production of inhibitory activity. Only the retinoic-acid-treated cells produce a potent angio-inhibitory activity that is able to block in vitro migration of endothelial cells toward tumor cell conditioned media and to halt neovascularization induced by such media in the rat cornea. Anti-angiogenic activity is induced in the tumor cells by low doses of retinoids in the absence of toxicity with a kinetics that suggest that it could be contributing to the effectiveness of the retinoids as chemopreventive agents.
维甲酸作为上消化道鳞状细胞癌化学预防剂已显示出巨大潜力。然而，它们阻止新肿瘤产生的确切机制尚不清楚。在此，我们报告，以临床可达到的剂量10(-6)mol/L或更低使用的13-顺式和全反式维甲酸，可直接且特异性地影响从口腔鳞状细胞癌培养的细胞系，诱导它们从促血管生成表型转变为抗血管生成表型。尽管经维甲酸处理和未处理的肿瘤细胞产生相同量的白细胞介素-8（此类肿瘤系产生的新血管形成的主要诱导剂），但它们在抑制活性的产生方面有所不同。只有经维甲酸处理的细胞产生一种有效的血管抑制活性，能够在体外阻断内皮细胞向肿瘤细胞条件培养基的迁移，并阻止此类培养基在大鼠角膜中诱导的新血管形成。低剂量维甲酸在无毒性的情况下在肿瘤细胞中诱导抗血管生成活性，其动力学表明这可能有助于维甲酸作为化学预防剂的有效性。
