Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers

Takashi Sugino, Tomiko Yamaguchi, Go Ogura, Atsuko Saito, Takeaki Hashimoto, Nobuo Hoshi, Sakaya Yoshida, Steve Goodison, Toshimitsu Suzuki

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Background: We have previously described an alternative invasion-independent pathway of cancer metastasis in a murine mammary tumor model. This pathway is initiated by intravasation of tumor nests enveloped by endothelial cells of sinusoidal vasculature within the tumor. In this study, we examined whether evidence for the invasion-independent pathway of metastasis is present in human cancers. Methods: Archival specimens of 10 common types of human cancers were examined for the presence of sinusoidal vasculature enveloping tumor nests and subsequently generated endothelial-covered tumor emboli in efferent veins. Results: A percentage of tumor emboli in all cancers was found to be enveloped by endothelial cells, but these structures were particularly prevalent in renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. A common feature of the vasculature in these tumors was the presence of dilated sinusoid-like structures surrounding tumor nests. A high mean vascular area within tumors, an indication of sinusoidal vascular development, was significantly related to the presence of endothelial-covered tumor emboli. Conclusions: These results suggest that an invasion-independent metastatic pathway is possible in a wide variety of human cancers. Further investigation of this phenomenon may present new therapeutic strategies for the amelioration of cancer metastasis.

Original languageEnglish (US)
Article number9
JournalBMC Medicine
StatePublished - Apr 5 2004

ASJC Scopus subject areas

  • General Medicine


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