TY - JOUR
T1 - Molecular mechanisms of cancer metastasis via the lymphatic versus the blood vessels
AU - Leong, Stanley P.
AU - Naxerova, Kamila
AU - Keller, Laura
AU - Pantel, Klaus
AU - Witte, Marlys
N1 - Funding Information:
Klaus Pantel and Catherine Alix-Panabières received funding from the European IMI research project CANCER-ID (115749-CANCER-ID). Klaus Pantel and Sabine Riethdorf received funding from the Deutsche Krebshilfe (Nr. 70112504). Klaus Pantel has received research funding from the Deutsche Forschungsgemeinschaft (DFG) SPP2084 µBone and ERC Advanced Investigator Grant INJURMET (Nr. 834974). L.K and K.P were financially supported by KMU-innovativ-23 n 031B0843D.
Publisher Copyright:
© 2021, The Author(s).
PY - 2022/2
Y1 - 2022/2
N2 - Cancer metastasis is the process by which primary cancer cells invade through the lymphatic or blood vessels to distant sites. The molecular mechanisms by which cancer cells spread either through the lymphatic versus blood vessels or both are not well established. Two major developments have helped us to understand the process more clearly. First, the development of the sentinel lymph node (SLN) concept which is well established in melanoma and breast cancer. The SLN is the first lymph node in the draining nodal basin to receive cancer cells. Patients with a negative SLN biopsy show a significantly lower incidence of distant metastasis, suggesting that the SLN may be the major gateway for cancer metastasis in these cancer types. Second, the discovery and characterization of several biomarkers including VEGF-C, LYVE-1, Podoplanin and Prox-1 have opened new vistas in the understanding of the induction of lymphangiogenesis by cancer cells. Cancer cells must complete multiple steps to invade the lymphatic system, some of which may be enabled by the evolution of new traits during cancer progression. Thus, cancer cells may spread initially through the main gateway of the SLN, from which evolving cancer clones can invade the blood vessels to distant sites. Cancer cells may also enter the blood vessels directly, bypassing the SLN to establish distant metastases. Future studies need to pinpoint the molecules that are used by cancer cells at different stages of metastasis via different routes so that specific therapies can be targeted against these molecules, with the goal of stopping or preventing cancer metastasis.
AB - Cancer metastasis is the process by which primary cancer cells invade through the lymphatic or blood vessels to distant sites. The molecular mechanisms by which cancer cells spread either through the lymphatic versus blood vessels or both are not well established. Two major developments have helped us to understand the process more clearly. First, the development of the sentinel lymph node (SLN) concept which is well established in melanoma and breast cancer. The SLN is the first lymph node in the draining nodal basin to receive cancer cells. Patients with a negative SLN biopsy show a significantly lower incidence of distant metastasis, suggesting that the SLN may be the major gateway for cancer metastasis in these cancer types. Second, the discovery and characterization of several biomarkers including VEGF-C, LYVE-1, Podoplanin and Prox-1 have opened new vistas in the understanding of the induction of lymphangiogenesis by cancer cells. Cancer cells must complete multiple steps to invade the lymphatic system, some of which may be enabled by the evolution of new traits during cancer progression. Thus, cancer cells may spread initially through the main gateway of the SLN, from which evolving cancer clones can invade the blood vessels to distant sites. Cancer cells may also enter the blood vessels directly, bypassing the SLN to establish distant metastases. Future studies need to pinpoint the molecules that are used by cancer cells at different stages of metastasis via different routes so that specific therapies can be targeted against these molecules, with the goal of stopping or preventing cancer metastasis.
KW - Cancer metastasis
KW - Cancer metastasis through the blood vessels
KW - Cancer metastasis through the lymphatic vessels
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U2 - 10.1007/s10585-021-10120-z
DO - 10.1007/s10585-021-10120-z
M3 - Review article
C2 - 34767139
AN - SCOPUS:85118921428
SN - 0262-0898
VL - 39
SP - 159
EP - 179
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 1
ER -