Barsky S H, Gopalakrishna R
Cancer Res. 1987 Mar 15;47(6):1663-7.
BL6 melanoma cells injected s.c. in 18-month C57 BL/6 mice elicit a markedly fibrotic response similar in myofibroblast and collagen composition to that characterizing the desmoplastic response of human breast carcinoma. This host response can be quantitated by measuring hydroxyproline (total collagen) and incorporation of i.p.-injected [14C]proline into collagenase-sensitive protein (new collagen synthesis). Inhibition (70%) of the desmoplastic response can be achieved by daily injections of L-3,4-dehydroproline. Inhibiting the response in this manner promotes local invasion of tumor and increases the incidence of spontaneous pulmonary metastasis. 10(5) BL6 melanoma cells produce tumor nodules with a mean diameter of 1.5 +/- 0.5 cm and mean collagen content of 36 +/- 15 mg/g wet tissue at 4 weeks and 10% incidence of pulmonary metastasis at 7 weeks. L-3,4-dehydroproline produces nodules with a mean diameter of 2.3 +/- 0.5 cm and mean collagen content of 12 +/- 2 mg/g with a 40% incidence of metastasis. L-3,4-dehydroproline exerts a selective effect on myofibroblast collagen synthesis in vitro and no effect on [3H]thymidine uptake, doubling time, and viability of BL6 cells and myofibroblasts. Furthermore, this drug exerts no effect on BL6 invasion and metastasis in 6-week C57 BL/6 mice, hosts which exhibit a negligible desmoplastic response.
将BL6黑色素瘤细胞皮下注射到18个月大的C57 BL/6小鼠体内，会引发明显的纤维化反应，其肌成纤维细胞和胶原蛋白组成与人类乳腺癌的促结缔组织增生反应相似。这种宿主反应可以通过测量羟脯氨酸（总胶原蛋白）以及将腹腔注射的[14C]脯氨酸掺入对胶原酶敏感的蛋白质（新胶原蛋白合成）来定量。通过每日注射L-3,4-脱氢脯氨酸可实现对促结缔组织增生反应的抑制（70%）。以这种方式抑制反应会促进肿瘤的局部侵袭并增加自发性肺转移的发生率。10(5)个BL6黑色素瘤细胞在4周时产生平均直径为1.5±0.5厘米、平均胶原蛋白含量为36±15毫克/克湿组织的肿瘤结节，7周时肺转移发生率为10%。L-3,4-脱氢脯氨酸产生的结节平均直径为2.3±0.5厘米，平均胶原蛋白含量为12±2毫克/克，转移发生率为40%。L-3,4-脱氢脯氨酸在体外对肌成纤维细胞胶原蛋白合成具有选择性作用，对BL6细胞和肌成纤维细胞的[3H]胸苷摄取、倍增时间和活力没有影响。此外，这种药物对6周龄C57 BL/6小鼠（表现出可忽略不计的促结缔组织增生反应的宿主）的BL6侵袭和转移没有影响。
