Morris V L, Koop S, MacDonald I C, Schmidt E E, Grattan M, Percy D, Chambers A F, Groom A C
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Clin Exp Metastasis. 1994 Nov;12(6):357-67. doi: 10.1007/BF01755879.
We examined the extravasation and subsequent migration and growth of murine mammary tumor cell lines (D2A1 and D2.OR) which differ in their metastatic ability in lung and liver, invasiveness in vitro and expression of the cysteine proteinase cathepsin L. In light of the differences in invasiveness and cathepsin L expression, we hypothesized that during hematogenous metastasis the two cell lines would differ primarily in their ability to extravasate. We used in vivo videomicroscopy of mouse liver and chick embryo chorioallantoic membrane to examine the process and timing of extravasation and subsequent steps in metastasis for these cell lines. In contrast to our expectations, no differences were found between the cell lines in either the timing or mechanism of extravasation, at least 95% of cells having extravasated by 3 days after injection. However, after extravasation, the more metastatic and invasive D2A1 cells showed a greater ability to migrate to sites which favor tumor growth and to replicate to form micrometastases. These studies point to post-extravasation events (migration and growth) as being critical in metastasis formation.
我们研究了小鼠乳腺肿瘤细胞系（D2A1和D2.OR）的外渗以及随后的迁移和生长情况，这两种细胞系在肺和肝中的转移能力、体外侵袭性以及半胱氨酸蛋白酶组织蛋白酶L的表达方面存在差异。鉴于侵袭性和组织蛋白酶L表达的差异，我们推测在血行转移过程中，这两种细胞系主要在外渗能力上存在差异。我们利用小鼠肝脏和鸡胚绒毛尿囊膜的体内视频显微镜技术，来研究这些细胞系外渗的过程和时间以及转移的后续步骤。与我们的预期相反，在细胞系之间，无论是外渗的时间还是机制都没有发现差异，至少95%的细胞在注射后3天内已外渗。然而，外渗后，转移性和侵袭性更强的D2A1细胞表现出更强的迁移到有利于肿瘤生长的部位并进行增殖以形成微转移灶的能力。这些研究表明，外渗后事件（迁移和生长）在转移形成过程中至关重要。
