INHIBITION OF B16 MELANOMA METASTASIS BY ADMINISTRATION OF G(M3)- OR GG3- LIPOSOMES - BLOCKING ADHESION OF MELANOMA-CELLS TO ENDOTHELIAL-CELLS (ANTIADHESION THERAPY) VIA INHIBITION OF G(M3)-GG3CER OR G(M3)-LACCER INTERACTION

Author(s):  
E OTSUJI ◽  
YS PARK ◽  
K TASHIRO ◽  
N KOJIMA ◽  
T TOYOKUNI ◽  
...  
2015 ◽  
Vol 112 (8) ◽  
pp. 2521-2526 ◽  
Author(s):  
Dawn R. Christianson ◽  
Andrey S. Dobroff ◽  
Bettina Proneth ◽  
Amado J. Zurita ◽  
Ahmad Salameh ◽  
...  

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial–melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell–cell interactions at the lymphatic–tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2697
Author(s):  
Thouria Bourhim ◽  
Myra O. Villareal ◽  
Chemseddoha Gadhi ◽  
Hiroko Isoda

The beneficial effect on health of argan oil is recognized worldwide. We have previously reported that the cake that remains after argan oil extraction (argan press-cake or APC) inhibits melanogenesis in B16 melanoma cells in a time-dependent manner without cytotoxicity. In this study, the global gene expression profile of B16 melanoma cells treated with APC extract was determined in order to gain an understanding of the possible mechanisms of action of APC. The results suggest that APC extract inhibits melanin biosynthesis by down-regulating microphthalmia-associated transcription factor (Mitf) and its downstream signaling pathway through JNK signaling activation, and the inhibition of Wnt/β-catenin and cAMP/PKA signaling pathways. APC extract also prevented the transport of melanosomes by down-regulating Rab27a expression. These results suggest that APC may be an important natural skin whitening product and pharmacological agent used for clinical treatment of pigmentary disorders.


2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110192
Author(s):  
Yuki Ohno ◽  
Shiori Kondo ◽  
Kiho Tajima ◽  
Toshiyuki Shibata ◽  
Tomohiro Itoh

Phlorotannins isolated from brown algae, such as Eisena bicyclis, have positive physiological effects, including anti-cancer, anti-inflammatory, and anti-Alzheimer’s disease. Although phlorotannins have been shown to inhibit tyrosinase, an enzyme essential for melanogenesis, their effect on melanogenesis remains unexplored. Thus, we isolated phlorotannins from E. bicyclis and examined their effects on α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in murine B16 melanoma cells. Both fucofuroeckol-A (FF-A) and phlorofucofuroeckol-A (PFF-A) suppressed α-MSH-induced melanogenesis. Neither inhibited human tyrosinase (TYR) activity, but both inhibited tyrosinase-related protein-2 activity. FF-A downregulated the expression of microphthalmia-associated transcription factor and TYR, which subsequently suppressed melanin production. These results suggest that phlorotannins could be beneficial as melanin control drugs for hyperpigmentation disorders.


Lipids ◽  
2010 ◽  
Vol 45 (5) ◽  
pp. 401-407 ◽  
Author(s):  
Jeung-Hyun Koo ◽  
Ikjae Lee ◽  
Seok-Kweon Yun ◽  
Han-Uk Kim ◽  
Byung-Hyun Park ◽  
...  

1997 ◽  
Vol 93 (1-3) ◽  
pp. 107-117 ◽  
Author(s):  
Jun Kanno ◽  
Atsuko Wakikawa ◽  
Masanori Utsuyama ◽  
Katsuiku Hirokawa

1990 ◽  
Vol 22 (4) ◽  
pp. 213-218 ◽  
Author(s):  
Y. Sakaguchi ◽  
Y. Emi ◽  
Y. Maehara ◽  
S. Kohnoe ◽  
K. Sugimachi

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