Marvin M R, Southall J C, Trokhan S, DeRosa C, Chabot J
Department of Surgery, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
J Surg Res. 1998 Dec;80(2):143-8. doi: 10.1006/jsre.1998.5322.
Adhesion molecules play an integral role in tumor growth, invasion, and metastasis and have been shown to influence the immune response to malignant cells. The interaction of intercellular adhesion molecule-1 (ICAM-1) with lymphocyte function antigen-1 (LFA-1) is important for the adhesion of leukocytes, monocytes and lymphocytes to endothelial cells in vitro and in vivo. In order to explore the role of the ICAM-1/LFA-1 interaction in liver metastases, we utilized homozygous deletionally mutant (gene knockout) mice for ICAM-1 or LFA-1 which had been derived from the C57BL6/J background.
Wild-type C57BL6/J mice were used as controls. Animals were anesthetized and underwent a 1-cm midline lower abdominal incision. The ileocolic vein was identified and B16 melanoma cells (10(4)) were injected. The incisions were closed with skin clips. Two weeks following surgery, mice were sacrificed and their livers resected for gross and histological analysis.
LFA-1 deficient mice developed 13 times the number of metastases compared to wild-type controls and ICAM-1 deficient mice developed 7 times that number [13.5 (n = 17) vs 1.0 (n = 19) and 36 (n = 10) vs 5.0 (n = 16), P values of 0.0003 and 0.0002 by Wilcoxon Rank Sum Test, respectively]: Histologically, multiple areas of inflammatory cells consisting of T-cells and macrophages were noted in wild-type mice. Only sparse inflammatory cells were noted surrounding the metastases in the null mice.
Liver metastases of the B16 melanoma are markedly enhanced in ICAM-1 null and LFA-1 null mice. The ICAM-1/LFA-1 interaction is crucial to the immune response to liver metastases.
黏附分子在肿瘤生长、侵袭和转移过程中发挥着不可或缺的作用，并且已被证明会影响对恶性细胞的免疫反应。细胞间黏附分子-1（ICAM-1）与淋巴细胞功能相关抗原-1（LFA-1）的相互作用对于白细胞、单核细胞和淋巴细胞在体外和体内与内皮细胞的黏附至关重要。为了探究ICAM-1/LFA-1相互作用在肝转移中的作用，我们使用了源自C57BL6/J背景的ICAM-1或LFA-1纯合缺失突变（基因敲除）小鼠。
野生型C57BL6/J小鼠用作对照。动物麻醉后，在下腹部做一个1厘米的中线切口。识别出回结肠静脉并注射B16黑色素瘤细胞（10⁴个）。切口用皮肤夹闭合。手术后两周，处死小鼠并切除肝脏进行大体和组织学分析。
与野生型对照相比，LFA-1缺陷小鼠发生转移的数量是其13倍，ICAM-1缺陷小鼠发生转移的数量是其7倍[分别为13.5（n = 17）对1.0（n = 19）和36（n = 10）对5.0（n = 16），通过Wilcoxon秩和检验，P值分别为0.0003和0.0002]：组织学上，在野生型小鼠中观察到由T细胞和巨噬细胞组成的多个炎症细胞区域。在基因敲除小鼠的转移灶周围仅观察到稀疏的炎症细胞。
ICAM-1基因敲除和LFA-1基因敲除小鼠中B16黑色素瘤的肝转移明显增强。ICAM-1/LFA-1相互作用对于肝转移的免疫反应至关重要。
