An invasion-independent pathway of blood-borne metastasis: a new murine mammary tumor model.
It is generally believed that active invasion by cancer cells is essential to the metastatic process. In this report, we describe a murine mammary tumor (MCH66) model of metastasis that does not require invasion into the vascular wall of both the primary tumor and the target organ, in this case, the lung. The process involves intravasation of tumor nests surrounded by sinusoidal blood vessels, followed by intravascular tumor growth in the lung, without penetration of the vascular wall during the process. Comparative studies using a nonmetastatic MCH66 clone (MCH66C8) and another highly invasive metastatic cell line (MCH416) suggested that high angiogenic activity and sinusoidal remodeling of tumor blood vessels were prerequisites for MCH66 metastasis. Differential cDNA analysis identified several genes that were overexpressed by MCH66, including genes for the angiogenesis factor pleiotrophin, and extracellular matrix-associated molecules that may modulate the microenvironment toward neovascularization. Our analyses suggest that tumor angiogenesis plays a role in the induction of invasion-independent metastasis. This model should prove useful in screening and development of new therapeutic agents for cancer metastasis.
Sugino
Takashi
T
Department of Pathology, School of Medicine, Fukushima Medical University, Fukushima City, Japan. sugino@fmu.ac.jp
Kusakabe
Takashi
T
Hoshi
Nobuo
N
Yamaguchi
Tomiko
T
Kawaguchi
Takanori
T
Goodison
Steve
S
Sekimata
Masayuki
M
Homma
Yoshimi
Y
Suzuki
Toshimitsu
T
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C066845:pleiotrophin; D018093:Gelatinases