Liver colonization competence governs colon cancer metastasis
Liver colonization competence governs colon cancer metastasis
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DOI：
10.1073/pnas.92.26.12085
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发表时间：
1995-12-19
影响因子：
11.1
通讯作者：
Hoffman, RM
中科院分区：
文献类型：
--
作者：
Kuo, TH;Kubota, T;Hoffman, RM
转移的肿瘤会转移到首选的靶器官。为了解释这种明显的特异性，佩吉特在>100年前提出了他的种子和土壤假说;即，来自给定肿瘤的细胞将仅“播种”由某些器官提供的有利的“土壤”。该假设意味着癌细胞必须在靶器官中找到合适的“土壤”-即，一个支持定植的基因--让转移发生。我们在这份报告中证明，人类结肠癌细胞在肝组织中定植的能力决定了特定结肠癌是否转移。在本研究中使用的模型中，通过手术原位植入将人结肠肿瘤作为完整组织块移植到裸鼠结肠中。这些植入的肿瘤密切模拟原始人类患者肿瘤的转移行为，并且明显转移或非转移到肝脏。两类肿瘤在局部侵入组织和血管中是相同的。然而，当直接注射到裸鼠肝脏中时，来自每类肿瘤的细胞表现非常不同。只有来自转移性肿瘤的细胞能够在直接肝内注射后定植。来自转移性肿瘤的组织块直接附着于肝脏导致定殖，而非转移性肿瘤组织块即使在组织块本身内发生一些生长也不导致定殖。（注射）和甚至粘附到转移性靶器官（块）不足以转移，结果表明，在人类结肠癌的转移中，肝脏的定殖能力是控制步骤。
Tumors that metastasize do so to preferred target organs, To explain this apparent specificity, Paget, >100 years ago, formulated his seed and soil hypothesis; i,e., the cells from a given tumor would ''seed'' only favorable ''soil'' offered by certain organs, The hypothesis implies that cancer cells must find a suitable ''soil'' in a target organ - i.e., one that supports colonization - for metastasis to occur. We demonstrate in this report that ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer is metastatic. In the model used in this study, human colon tumors are transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation. These implanted tumors closely simulate the metastatic behavior of the original human patient tumor and are clearly metastatic or nonmetastatic to the liver, Both classes of tumors were equally invasive locally into tissues and blood vessels, However, the cells from each class of tumor behave very differently when directly injected into nude mouse livers, Only cells from metastasizing tumors are competent to colonize after direct intrahepatic injection, Also, tissue blocks from metastatic tumors affixed directly to the liver resulted in colonization, whereas no colonization resulted from nonmetastatic tumor tissue blocks even though some growth occurred within the tissue block itself, Thus, local invasion (injection) and even adhesion to the metastatic target organ (blocks) are not sufficient for metastasis, The results suggest that the ability to colonize the liver is the governing step in the metastasis of human colon cancer.