Open Access Open Badges Research article

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

Takashi Sugino1*, Tomiko Yamaguchi1, Go Ogura1, Atsuko Saito2, Takeaki Hashimoto1, Nobuo Hoshi1, Sayaka Yoshida3, Steve Goodison4 and Toshimitsu Suzuki1

Author Affiliations

1 Department of Pathology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan

2 Pathology Division, Jusendo General Hospital, Koriyama, 963-8002, Japan

3 Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan

4 Department of Pathology, University of Florida, Jacksonville, FL 32209-6511, USA

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BMC Medicine 2004, 2:9  doi:10.1186/1741-7015-2-9

Published: 5 April 2004



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.


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.


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.


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.