Journal of Leukocyte Biology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published online as doi:10.1189/jlb.1107776 on June 10, 2008

Published online before print June 10, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.1107776v1
84/4/965    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Fang, L.
Right arrow Articles by Hwang, S. T.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fang, L.
Right arrow Articles by Hwang, S. T.
(Journal of Leukocyte Biology. 2008;84:965-972.)
© 2008 by Society for Leukocyte Biology

CCR7 regulates B16 murine melanoma cell tumorigenesis in skin

Lei Fang, Vivian C. Lee, Emily Cha, Hong Zhang and Sam T. Hwang1

Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

1 Correspondence: Dermatology Branch, CCR, NCI, 10 Center Dr., Bldg. 10/Rm. 12N238, Bethesda, MD 20892-1908, USA. E-mail: hwangs{at}mail.nih.gov

ABSTRACT

Tumor cell-associated chemokine receptors play distinct roles in cancer biology, including enhancement of lymph node (LN) metastasis. To determine if CCR7 influences tumor formation in skin, we inoculated B16 cells transduced with CCR7 and luciferase (CCR7-luc-B16) or with retroviral vector and luciferase (pLNCX2-luc-B16) into ear skin and footpads of wild-type (WT) mice. In contrast to pLNCX2-luc-B16 cells, 97% of CCR7-luc-B16 cell-inoculated mice formed skin tumors as well as cervical LN metastases by Day 21 following ear inoculation. CCR7-expressing and control B16 cells, however, formed tumors of similar size and with high-efficiency in SCID-beige mice. Cells from both lines accumulated in the skin of WT mice in similar numbers until Day 7. By Day 11, however, control cells decreased tenfold, whereas CCR7-luc-B16 cells formed small tumor nodules. Tumor cells were infrequently detected in draining cervical LNs up to 11 days after injection of both cell lines, but stable nodal metastases were only observed after CCR7-luc-B16 ear tumors had been established (~Day 21). ELISPOT assays revealed that IFN-{gamma}-producing cells in draining LNs from CCR7-luc-B16-injected ears were reduced through Day 7. After footpad injection, tumor formation by CCR7-expressing B16 cells was enhanced only with small, initial tumor cell inocula. With larger inocula, tumor formation was equivalent, but the numbers of tumor-infiltrating leukocytes were reduced by approximately sixfold in CCR7-B16 tumors compared with pLNCX2-B16 tumors of equal size. IFN-{gamma} and CXCL10 were reduced 35- and sixfold, respectively, in CCR7-B16 cell tumors (vs. control tumors). Thus, CCR7 expression enhances tumorigenesis in addition to facilitating LN metastasis.

Key Words: chemokine • tumor immunology






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Society for Leukocyte Biology.