Tumor-induced lymphangiogenesis in cervical lymph nodes in oral melanoma-bearing miceReport as inadecuate

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Journal of Experimental and Clinical Cancer Research

, 31:83

First Online: 02 October 2012Received: 12 September 2012Accepted: 29 September 2012


BackgroundMetastasis via the lymphatic system is promoted by lymphangiogenesis. Alterations of the lymphatic channels during the progression of metastasis to regional lymph nodes LNs remain unexplored. To examine whether tumor-induced LN lymphangiogenesis controls metastasis to regional LNs, we investigated cervical LN metastasis in a mouse model of oral melanoma.

MethodsInjection of B16F10 melanoma cells into mouse tongues replicated spontaneous cervical LN metastasis. We performed histological, immunofluorescent, and histomorphometric analyses of tumor-reactive lymphadenopathy and lymphangiogenesis in tumor-associated LNs. We investigated the expression of vascular endothelial growth factor VEGF-C and its receptor, VEGF receptor-3 VEGFR-3, in tumor cells and tissues, and LNs by reverse transcription polymerase chain reaction and immunofluorescence.

ResultsTumor-associated LNs comprised sentinel LNs SLNs before and after tumor cell invasion tumor-bearing SLNs, and LNs adjacent or contralateral to tumor-bearing SLNs. Extensive lymphangiogenesis appeared in SLNs before evidence of metastasis. After metastasis was established in SLNs, both LNs adjacent and contralateral to tumor-bearing SLNs demonstrated lymphangiogenesis. Interaction between VEGF-C-positive melanoma cells and VEGFR-3-positive lymphatic vessels was evident in tumor-associated LNs.

ConclusionsLN lymphangiogenesis contributes a progression of tumor metastasis from SLNs to other regional LNs.

KeywordsSentinel lymph node Tumor-bearing lymph node Oral melanoma Lymphangioegnesis Lymphatic metastasis AbbreviationsLNLymph node

SLNSentinel lymph node

VEGFVascular endothelial growth factor

VEGFRVEGF receptor

LYVE-1Lymphatic Vessel Endothelial hyaluronan receptor 1

DMEMDulbecoo’s Modified Eagle’s medium

PBSPhosphate-buffered Saline

HEHematoxylin and Eosin

TRP-1Tyrosinase-related Protein 1

IgGImmunoglobulin G Flt-4: Fms-related tyrosine kinase 4

RT-PCRReverse Transcription-polymerase Chain Reaction.

Electronic supplementary materialThe online version of this article doi:10.1186-1756-9966-31-83 contains supplementary material, which is available to authorized users.

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Author: Ryuki Ozasa - Jun Ohno - Teruaki Iwahashi - Kunihisa Taniguchi

Source: https://link.springer.com/

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