Induced lymphatic sinus hyperplasia in sentinel lymph nodes by VEGF-C             as the earliest premetastatic indicator.
Research on tumor-induced lymphangiogenesis has predominantly focused on             alterations and abnormal growth of peritumoral and intratumoral lymphatic vessels.             However, recent evidence indicates that lymphangiogenesis of sentinel lymph nodes             might also contribute to cancer progression. In clinical oncology, the sentinel             lymph nodes play an important role in diagnosis, staging and management of disease.             The prognostic value that may be placed in the analysis of various parameters             in tumor-free lymph nodes is still under debate. We, therefore, chose to investigate             genetically fluorescent MDA-MB-435/green fluorescent protein human cancer cells             transfected to overexpress VEGF-C in a nude mouse model and investigated metastasis,             lymph node lymphangiogenesis, lymph node angiogenesis and size of sentinel lymph             nodes. The nature of MDA-MB-435, identified as a breast cancer cell line for several             decades, has recently been reidentified as being from melanoma origin. Vascular             endothelial growth factor-C overexpression induced early metastasis and significantly             increased the lymphatic vessel area in sentinel lymph nodes even before the tumor             metastasis. At early time-points, expansion of the lymphatic network was observed             even though no difference of blood vessel area and lymph node size was detected.             These results suggest that primary tumors -via secretion of VEGF-C- can induce             hyperplasia of the sentinel lymph node lymphatic vessel network and thereby promote             their further spread. In cases of tumor-free lymph nodes the increased lymphatic             network of sentinel lymph nodes is a very early premetastatic sign and may provide             a new prognostic indicator and target for aggressive diseases.
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. rliersch@uni-muenster.de
Ruediger
R
Liersch
Satoshi
S
Hirakawa
Wolfgang E
WE
Berdel
Rolf M
RM
Mesters
Michael
M
Detmar
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
D015415:Biomarkers; D042582:Vascular Endothelial Growth Factor C