HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: 2432060604v1 243/3/703    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kruskal, J. B. Articles by Goldberg, S. N. Search for Related Content PubMed PubMed Citation Articles by Kruskal, J. B. Articles by Goldberg, S. N.

Hepatic Colorectal Cancer Metastases: Imaging Initial Steps of Formation in Mice¹

¹ From the Departments of Radiology (J.B.K., A.A., H.K., M.E., S.N.G.) and Medicine (S.C.R.), Beth Israel Deaconess Medical Center and Harvard Medical School, West Clinical Center-CC302B, 1 Deaconess Rd, Boston MA 02215; and Departments of Surgery and Biomedical Sciences, Creighton University, Omaha, Neb (P.T.). From the 2005 RSNA Annual Meeting. Received April 4, 2006; revision requested June 20; revision received July 14; final version accepted September 8. Supported by grants from the National Institutes of Health (R21 CA89634-JK, HL57307, and HL63972-SCR). J.B.K. supported by the RSNA Research and Education Foundation (RSNA Scholar Award) and the Society of Gastrointestinal Radiologists (Philip H. Meyers Research Award). Address correspondence to J.B.K. (e-mail: jkruskal{at}bidmc.harvard.edu).

Purpose: To prospectively use optical imaging to study the cell-specific mechanisms of entrapment and subsequent growth of two human colon cancer cell lines differing in their propensity to form hepatic metastases.

Materials and Methods: In this Animal Care Committee–approved study, intravital optical imaging was performed in exteriorized livers of three groups of mice after intrasplenic inoculation of human colon cancer cells. Group 1 mice (control group; n = 12) received a cell-maintaining solution only. Groups 2 and 3 (n = 12 in each) were administered poorly (MIP-101 colon cancer cells) or highly (CX-1 colon cancer cells) metastatic cells. Imaging was performed on postinoculation days 0, 1, 3, and 6 to document sites and mechanisms of tumor cell entrapment and presence and sites of endothelial cell activation and of tumor cell interactions with systemic macrophages and Kupffer cells. Fluorescence intensity of Kupffer cells was compared by using the Mann-Whitney test. Immunohistochemistry served as the reference standard for all in vivo observations.

Results: Whereas both MIP-101 and CX-1 colon cancer cells adhered to periportal Kupffer cells, the CX-1 cells resulted in Kupffer cell activation, evidenced in vivo by increased visible peroxidase activity (P < .05). Only CX-1 cells were associated with subsequent downstream endothelial cell activation, evidenced by in vivo expression of E-selectin. By day 6, regression of periportal MIP-101 tumor growth correlated with ingrowth of systemic macrophages, while CX-1 tumor growth, originating in the outflow venous regions, correlated with translobular migration and ingrowth of activated Kupffer cells.

Conclusion: Formation of hepatic colon cancer metastases is cancer cell–type specific, with cell lines differing in their mechanisms and intrahepatic locations of initial entrapment and Kupffer cell activation and subsequent growth.

© RSNA, 2007