Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses

Suvendu Das, Eliana Sarrou, Simona Podgrabinska, Melanie Cassella, Sathish Kumar Mungamuri, Nikki Feirt, Ronald Gordon, Chandandeep S. Nagi, Yarong Wang, David R. Entenberg, John S. Condeelis, Mihaela Skobe

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Lymphatic vessels are thought to contribute to metastasis primarily by serving as a transportation system. It is widely believed that tumor cells enter lymph nodes passively by the flow of lymph. We demonstrate that lymph node lymphatic sinuses control tumor cell entry into the lymph node, which requires active tumor cell migration. In human and mouse tissues, CCL1 protein is detected in lymph node lymphatic sinuses but not in the peripheral lymphatics. CCR8, the receptor for CCL1, is strongly expressed by human malignant melanoma. Tumor cell migration to lymphatic endothelial cells (LECs) in vitro is inhibited by blocking CCR8 or CCL1, and recombinant CCL1 promotes migration of CCR8+ tumor cells. The proinflammatory mediators TNF, IL-1β, and LPS increase CCL1 production by LECs and tumor cell migration to LECs. In a mouse model, blocking CCR8 with the soluble antagonist or knockdown with shRNA significantly decreased lymph node metastasis. Notably, inhibitionof CCR8 led to the arrest of tumor cells in the collecting lymphatic vessels at the junction with the lymph node subcapsular sinus. These data identify a novel function for CCL1-CCR8 in metastasis and lymph node LECs as a critical checkpoint for the entry of metastases into the lymph nodes.

Original languageEnglish (US)
Pages (from-to)1509-1528
Number of pages20
JournalJournal of Experimental Medicine
Volume210
Issue number8
DOIs
StatePublished - 2013

Fingerprint

Chemokine CCL1
Lymph Nodes
Neoplasms
Endothelial Cells
Neoplasm Metastasis
Cell Movement
Lymphatic Vessels
CCR8 Receptors
Lymph
Interleukin-1
Small Interfering RNA
Melanoma

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Das, S., Sarrou, E., Podgrabinska, S., Cassella, M., Mungamuri, S. K., Feirt, N., ... Skobe, M. (2013). Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses. Journal of Experimental Medicine, 210(8), 1509-1528. https://doi.org/10.1084/jem.20111627

Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses. / Das, Suvendu; Sarrou, Eliana; Podgrabinska, Simona; Cassella, Melanie; Mungamuri, Sathish Kumar; Feirt, Nikki; Gordon, Ronald; Nagi, Chandandeep S.; Wang, Yarong; Entenberg, David R.; Condeelis, John S.; Skobe, Mihaela.

In: Journal of Experimental Medicine, Vol. 210, No. 8, 2013, p. 1509-1528.

Research output: Contribution to journalArticle

Das, S, Sarrou, E, Podgrabinska, S, Cassella, M, Mungamuri, SK, Feirt, N, Gordon, R, Nagi, CS, Wang, Y, Entenberg, DR, Condeelis, JS & Skobe, M 2013, 'Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses', Journal of Experimental Medicine, vol. 210, no. 8, pp. 1509-1528. https://doi.org/10.1084/jem.20111627
Das, Suvendu ; Sarrou, Eliana ; Podgrabinska, Simona ; Cassella, Melanie ; Mungamuri, Sathish Kumar ; Feirt, Nikki ; Gordon, Ronald ; Nagi, Chandandeep S. ; Wang, Yarong ; Entenberg, David R. ; Condeelis, John S. ; Skobe, Mihaela. / Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses. In: Journal of Experimental Medicine. 2013 ; Vol. 210, No. 8. pp. 1509-1528.
@article{ea0606f55b984af7ad73a8c5bad3c0b7,
title = "Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses",
abstract = "Lymphatic vessels are thought to contribute to metastasis primarily by serving as a transportation system. It is widely believed that tumor cells enter lymph nodes passively by the flow of lymph. We demonstrate that lymph node lymphatic sinuses control tumor cell entry into the lymph node, which requires active tumor cell migration. In human and mouse tissues, CCL1 protein is detected in lymph node lymphatic sinuses but not in the peripheral lymphatics. CCR8, the receptor for CCL1, is strongly expressed by human malignant melanoma. Tumor cell migration to lymphatic endothelial cells (LECs) in vitro is inhibited by blocking CCR8 or CCL1, and recombinant CCL1 promotes migration of CCR8+ tumor cells. The proinflammatory mediators TNF, IL-1β, and LPS increase CCL1 production by LECs and tumor cell migration to LECs. In a mouse model, blocking CCR8 with the soluble antagonist or knockdown with shRNA significantly decreased lymph node metastasis. Notably, inhibitionof CCR8 led to the arrest of tumor cells in the collecting lymphatic vessels at the junction with the lymph node subcapsular sinus. These data identify a novel function for CCL1-CCR8 in metastasis and lymph node LECs as a critical checkpoint for the entry of metastases into the lymph nodes.",
author = "Suvendu Das and Eliana Sarrou and Simona Podgrabinska and Melanie Cassella and Mungamuri, {Sathish Kumar} and Nikki Feirt and Ronald Gordon and Nagi, {Chandandeep S.} and Yarong Wang and Entenberg, {David R.} and Condeelis, {John S.} and Mihaela Skobe",
year = "2013",
doi = "10.1084/jem.20111627",
language = "English (US)",
volume = "210",
pages = "1509--1528",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "8",

}

TY - JOUR

T1 - Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses

AU - Das, Suvendu

AU - Sarrou, Eliana

AU - Podgrabinska, Simona

AU - Cassella, Melanie

AU - Mungamuri, Sathish Kumar

AU - Feirt, Nikki

AU - Gordon, Ronald

AU - Nagi, Chandandeep S.

AU - Wang, Yarong

AU - Entenberg, David R.

AU - Condeelis, John S.

AU - Skobe, Mihaela

PY - 2013

Y1 - 2013

N2 - Lymphatic vessels are thought to contribute to metastasis primarily by serving as a transportation system. It is widely believed that tumor cells enter lymph nodes passively by the flow of lymph. We demonstrate that lymph node lymphatic sinuses control tumor cell entry into the lymph node, which requires active tumor cell migration. In human and mouse tissues, CCL1 protein is detected in lymph node lymphatic sinuses but not in the peripheral lymphatics. CCR8, the receptor for CCL1, is strongly expressed by human malignant melanoma. Tumor cell migration to lymphatic endothelial cells (LECs) in vitro is inhibited by blocking CCR8 or CCL1, and recombinant CCL1 promotes migration of CCR8+ tumor cells. The proinflammatory mediators TNF, IL-1β, and LPS increase CCL1 production by LECs and tumor cell migration to LECs. In a mouse model, blocking CCR8 with the soluble antagonist or knockdown with shRNA significantly decreased lymph node metastasis. Notably, inhibitionof CCR8 led to the arrest of tumor cells in the collecting lymphatic vessels at the junction with the lymph node subcapsular sinus. These data identify a novel function for CCL1-CCR8 in metastasis and lymph node LECs as a critical checkpoint for the entry of metastases into the lymph nodes.

AB - Lymphatic vessels are thought to contribute to metastasis primarily by serving as a transportation system. It is widely believed that tumor cells enter lymph nodes passively by the flow of lymph. We demonstrate that lymph node lymphatic sinuses control tumor cell entry into the lymph node, which requires active tumor cell migration. In human and mouse tissues, CCL1 protein is detected in lymph node lymphatic sinuses but not in the peripheral lymphatics. CCR8, the receptor for CCL1, is strongly expressed by human malignant melanoma. Tumor cell migration to lymphatic endothelial cells (LECs) in vitro is inhibited by blocking CCR8 or CCL1, and recombinant CCL1 promotes migration of CCR8+ tumor cells. The proinflammatory mediators TNF, IL-1β, and LPS increase CCL1 production by LECs and tumor cell migration to LECs. In a mouse model, blocking CCR8 with the soluble antagonist or knockdown with shRNA significantly decreased lymph node metastasis. Notably, inhibitionof CCR8 led to the arrest of tumor cells in the collecting lymphatic vessels at the junction with the lymph node subcapsular sinus. These data identify a novel function for CCL1-CCR8 in metastasis and lymph node LECs as a critical checkpoint for the entry of metastases into the lymph nodes.

UR - http://www.scopus.com/inward/record.url?scp=84883192541&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883192541&partnerID=8YFLogxK

U2 - 10.1084/jem.20111627

DO - 10.1084/jem.20111627

M3 - Article

C2 - 23878309

AN - SCOPUS:84883192541

VL - 210

SP - 1509

EP - 1528

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 8

ER -