INFLUENCE OF ORGAN ENVIRONMENT ON EXTRACELLULAR-MATRIX DEGRADATIVE ACTIVITY AND METASTASIS OF HUMAN COLON-CARCINOMA CELLS
INFLUENCE OF ORGAN ENVIRONMENT ON EXTRACELLULAR-MATRIX DEGRADATIVE ACTIVITY AND METASTASIS OF HUMAN COLON-CARCINOMA CELLS
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DOI：
10.1093/jnci/82.24.1890
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发表时间：
1990-12-19
期刊：
影响因子：
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通讯作者：
FIDLER, IJ
中科院分区：
文献类型：
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作者：
NAKAJIMA, M;MORIKAWA, K;FIDLER, IJ
原位移植人结肠癌细胞可用于研究转移性亚群的行为。我们观察到人结肠癌KM 12细胞的亲本系和变异体在BALB/c裸鼠皮下或盲肠壁内均具有致瘤性。然而，它们转移到远处器官部位的能力随生长部位而变化。皮下（SC）肿瘤不产生内脏转移，而盲肠肿瘤转移到区域肠系膜淋巴结和肝脏。为了研究器官环境对肿瘤细胞外基质降解活性的影响，我们将人结肠癌细胞接种到皮下组织或盲肠壁中，7周后分离并在无血清培养基中培养肿瘤。SC肿瘤的条件培养基含有极低水平的IV型胶原酶（明胶酶）和乙酰肝素酶（硫酸乙酰肝素特异性内切-β-D-葡萄糖醛酸酶），而盲肠壁肿瘤的培养基含有高水平的这两种酶。培养基的酶谱显示，盲肠内的人结肠癌分泌的潜伏和活性形式的92 kd IV型胶原酶的量是SC肿瘤的三倍以上。此外，只有条件培养基的盲肠内肿瘤含有潜伏和活性形式的64 kd IV型胶原酶。使用兔抗血清对72 kD的前胶原酶IV型的合成肽提出的组织化学分析表明，IV型胶原酶在盲肠内肿瘤;人结肠癌生长SC，但是，没有显着染色。这些结果表明，在器官环境中的因素可能会影响肿瘤细胞外基质降解酶的生产和分泌，这些因素可能会改变人结肠癌细胞在裸鼠体内的转移行为。[J Natl Cancer Inst 82：1890-1898，1990]
Orthotopic implantation of human colon carcinoma cells is useful for studying the behavior of metastatic subpopulations. We observed that the parental line and variants of human colon carcinoma KM12 cells were all tumorigenic following implantation into the subcutis or cecal wall of BALB/c nude mice. Their ability to metastasize to distant organ sites varied, however, with the site of growth. Subcutaneous (SC) tumors did not produce visceral metastases, whereas cecal tumors metastasized to the regional mesenteric lymph nodes and to the liver. To examine the influence of organ environment on the extracellular matrix-degrading activity of the tumors, we inoculated human colon carcinoma cells into the subcutis or cecal wall and after 7 weeks isolated and cultured the tumors in serum-free medium. The conditioned media of SC tumors contained very low levels of type IV collagenase (gelatinase) and heparanase (heparan sulfate-specific endo-β-D-glucuronidase) whereas the media of the cecal wall tumors contained high levels of both. Zymograms of the media revealed that the intracecal human colon carcinomas secreted more than three times the amount of latent and active forms of 92-kd type IV collagenase than did the SC tumors. Moreover, only the conditioned media of intracecal tumors contained latent and active forms of 64-kd type IV collagenase. Histochemical analysis using rabbit antiserum raised against the synthetic peptides of 72-kd procollagenase type IV showed type IV collagenase in the intracecal tumors; human colon carcinoma growing SC, however, were not stained significantly. These results suggest that factors in the organ environment may affect production and secretion of tumor extracellular matrix-degrading enzymes, and these factors may modify the metastatic behavior of human colon carcinoma cells in nude mice. [J Natl Cancer Inst 82:1890–1898, 1990]