title: Lymph node-independent liver metastasis in a model of metastatic colorectal cancer.
abstract: Deciphering metastatic routes is critically important as metastasis is a primary cause of cancer mortality. In colorectal cancer (CRC), it is unknown whether liver metastases derive from cancer cells that first colonize intestinal lymph nodes, or whether such metastases can form without prior lymph node involvement. A lack of relevant metastatic CRC models has precluded investigations into metastatic routes. Here we describe a metastatic CRC mouse model and show that liver metastases can manifest without a lymph node metastatic intermediary. Colorectal tumours transplanted onto the colonic mucosa invade and metastasize to specific target organs including the intestinal lymph nodes, liver and lungs. Importantly, this metastatic pattern differs from that observed following caecum implantation, which invariably involves peritoneal carcinomatosis. Anti-angiogenesis inhibits liver metastasis, yet anti-lymphangiogenesis does not impact liver metastasis despite abrogating lymph node metastasis. Our data demonstrate direct hematogenous spread as a dissemination route that contributes to CRC liver malignancy.
authors.affiliation: Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Ida B
authors.initials: IB
authors.lastname: Enquist
authors.affiliation: Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Zinaida
authors.initials: Z
authors.lastname: Good
authors.affiliation: Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Jubb
authors.affiliation: 1] Department of Antibody Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA [2] Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Germaine
authors.initials: G
authors.lastname: Fuh
authors.affiliation: Department of Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Junttila
authors.affiliation: Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Jackson
authors.affiliation: Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Leong
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D002277:Carcinoma / Q000556:secondary*; D002432:Cecum; D003106:Colon; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D045325:HCT116 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology*; D042583:Lymphangiogenesis / Q000187:drug effects; D008207:Lymphatic Metastasis; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000556:secondary*; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D042582:Vascular Endothelial Growth Factor C