Arguello F, Baggs R B, Eskenazi A E, Duerst R E, Frantz C N
Strong Children's Research Center, University of Rochester School of Medicine and Dentistry, NY 14642.
Int J Cancer. 1991 Jun 19;48(4):583-90. doi: 10.1002/ijc.2910480417.
We have examined with 19 tumor cell lines the discrete roles that vascular anatomy and tumor-cell-organ-affinity play in the development of metastases and their distribution among organs. Spontaneous metastases of B16-G3.26 melanoma cells from a primary tumor growing in the foot pad of mice, or experimental metastases 21 days after intravenous tumor-cell injection resulted in tumor colonies only in the lungs. In contrast, when the lung microvasculature was bypassed, and the same cells given by systemic intra-arterial (s.i.a.) injection, large tumor colonies developed selectively in the ovaries, adrenal glands and bones, but rarely in the lungs. When animals injected i.v. were allowed to live with lung metastases for a long period of time, small tumor colonies began to develop in extra-pulmonary organs with a distribution identical to that seen after s.i.a. injection. Seven murine tumor cell lines (previously characterized by their ability to colonize primarily the lungs after i.v. injection) and 7 of the 8 studied human tumor cell lines colonized different specific extra-pulmonary organs after s.i.a. injection, frequently producing metastatic syndromes commonly described in patients with cancer, but rarely seen in animal models of metastasis. These results suggest that metastatic cells, even those capable of colonizing specific organs, do not freely circulate in the blood stream and lodge in specific tissues. In contrast, the cells must establish a vascular route of access to the target organ, e.g., through the systemic circulation from metastatic tumors in the lungs. Two cell lines considered to be tumorigenic but non-metastatic failed to colonize the lungs or extra-pulmonary organs after i.v. injection, but readily colonized specific organs after s.i.a. injection. Thus, tumor cells considered to be non-metastatic may be indeed metastatic if they are provided with vascular access to an organ more congenial to their growth requirements.
我们用19种肿瘤细胞系研究了血管解剖结构和肿瘤细胞与器官的亲和性在转移发生及其在器官间分布过程中所起的不同作用。从小鼠脚垫原发性肿瘤自发转移的B16 - G3.26黑色素瘤细胞，或静脉注射肿瘤细胞21天后的实验性转移，仅在肺部形成肿瘤集落。相比之下，当绕过肺微血管，通过全身动脉内（s.i.a.）注射给予相同细胞时，大的肿瘤集落选择性地在卵巢、肾上腺和骨骼中形成，但很少在肺部形成。当静脉注射的动物带着肺转移瘤长期存活时，肺外器官开始出现小的肿瘤集落，其分布与s.i.a.注射后所见相同。7种小鼠肿瘤细胞系（以前的特征是静脉注射后主要在肺部定植）和8种研究的人类肿瘤细胞系中的7种，在s.i.a.注射后定植于不同的特定肺外器官，经常产生癌症患者中常见但在转移动物模型中很少见的转移综合征。这些结果表明，转移细胞，即使是那些能够定植于特定器官的细胞，也不会在血流中自由循环并在特定组织中着床。相反，细胞必须建立一条通往靶器官的血管通路，例如通过肺部转移瘤的体循环。两种被认为具有致瘤性但无转移能力的细胞系，静脉注射后未能在肺部或肺外器官定植，但s.i.a.注射后很容易在特定器官定植。因此，如果为被认为无转移能力的肿瘤细胞提供通往与其生长需求更相符的器官的血管通路，它们可能确实具有转移能力。
