The study on liver metastasis of colon cancer by using orthotopic inplantation.

肿瘤转移到首选的靶器官。为了解释这种明显的特异性，100年前，佩吉特提出了他的种子和土壤假说，即来自特定肿瘤的细胞只会“播种”特定器官提供的有利“土壤”。这个假设暗示癌细胞必须在目标器官中找到一个合适的“土壤”。这是一种支持定植的细胞，从而发生转移。我们在本报告中证明，人类结肠癌细胞定植肝组织的能力决定了特定结肠癌是否转移。在本研究使用的模型中，通过手术原位植入将人结肠肿瘤作为完整的组织块移植到裸鼠结肠中。这些植入的肿瘤与原始人类患者肿瘤的转移行为非常相似，并且明显转移到肝脏或未转移到肝脏。这两类肿瘤对局部组织和血管的侵袭性相同。然而，当直接注射到裸鼠肝脏时，来自不同类型肿瘤的细胞表现非常不同。直接肝内注射后，只有来自转移性肿瘤的细胞才有能力定植。此外，转移性肿瘤直接附着在肝脏上的组织块导致了定植，而非转移性肿瘤组织块即使在组织块内部发生了一些生长，也不会导致定植。因此，局部侵袭（注射）甚至粘附到转移靶器官（阻滞）都不足以发生转移。结果表明，在肝脏中定植的能力是人类结肠癌转移的控制步骤。我们利用免疫印迹法研究了整合素β 1亚基在51例结直肠癌组织中的表达，并确定了表达与临床分期的关系。与正常粘膜相比，β -亚基前体15例升高，2例降低，2例β -亚基表达降低。这些β 1亚基表达的改变与淋巴结转移和浸润深度显著相关（P<0.01）。这些结果提示整合素在结直肠癌的侵袭和转移中起重要作用。少

Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, >100years 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 behaviro 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 … More 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.2.We have investigated the expression of the integrin beta1 subunit in 51 colorectal cancer tissues using immunoblotting and have determined the relationship between expression and clinical stage. In comparison with normal mucosa the pre-beta-subunit (the precursor of beta1-subunit) was increased in 15 cases and decreased in two cases, and expression of the beta1-subunit was decreased in two cases. These alterations of expression of the beta1-subunit were significantly correlated with lymph node metastasis and depth of invasion (P<0.01). These results suggest that integrin plays an important role in the invasion and metastasis of colorectal cancer. Less