Metastasis is known to be the leading cause of cancer-related death. Cancer cells enter blood vessels and lymphatic vessels from where they first formed, travel along the blood and lymph flow to another organ or multiple organs, and multiply there. The most common cases are metastasis to lymph nodes where the flow of lymph fluid gathers, known as lymphatic metastasis. In addition, metastasis to places with abundant blood flow, such as the lungs, liver, brain, and bones, is known as hematogenous metastasis.
In this blog, I would like to share the study “Anti-Metastasis Effect of Fucoidan from Undaria pinnatifida Sporophylls in Mouse Hepatocarcinoma Hca-F Cell” by Peisheng Wang et al. The study evaluated how Undaria pinnatifida sporophylls (Ups-fucoidan), a sulfated polysaccharide with multiple biological activities than other fucoidans, prevent metastasis.
However, the information on the effect of Ups-fucoidan on tumor invasion and metastasis is yet to be confirmed. Hence, they investigated the impact of Ups fucoidan on cancer cell invasion and metastasis using a murine hepatoma Hca-F cell line with high invasive and lymphatic metastasis potential in vitro and in vivo.
First, they investigated the effects of Ups fucoidan on cancer cell invasion and metastasis using a murine hepatoma Hca-F cell line with high invasive and lymphatic metastasis potential in vitro and in vivo. Twenty-four 615 mice were assigned evenly to four groups. Hca-F cells (3×10 6, 30 μl) were inoculated (vaccinated) subcutaneously into the footpads of mice. After 48 hours, saline (NS, control group, 30 μl), Ups-fucoidan (treatment group, 125, 250 mg/kg, 30 μl), heparin (positive group, 125 μg/kg, 30 μl) are injected every other day.
Then, after four weeks, axillary lymph nodes were isolated, weighed, sectioned, and stained with HE. Cell proliferation after each Ups fucoidan treatment was statistically significant compared to untreated controls. (See figure 1A) Western blotting showed that Ups-fucoidan downregulated the expression levels of cyclin D1 and CDK4. (See Figure 1B) Ups-fucoidan can inhibit the proliferation of Hca-F cells.
Additionally, they investigated the effects of Ups-fucoidan on cancer cell invasion and metastasis using the mouse hepatoma Hca-F cell line, which has high invasiveness and lymph-metastatic potential in vitro and in vivo. Ups-fucoidan exerted a concentration- and time-dependent anti-tumor metastasis effect in vivo and inhibited the proliferation, migration, invasion, and adhesion capacity of the Hca-F cells in vitro. (See Figure 2B)
Western blotting and ELISA were used to assess the activity of the NF-κB-dependent PI3K/Akt and ERK signaling pathways and the critical factors involved. Expression of VEGFR-3, c-MET, p-PI3K, p-Akt, p-ERK1/2, and NF-κB was downregulated in Ups-fucoidan-treated cells. In addition, ELISA results showed that the levels of VEGF-C and HGF proteins in Ups-fucoidan-treated cells were lower (p<0.01) compared to controls. (See Figure 3C)
In some cancers, VEGF is commonly overexpressed, which means making too many copies of certain proteins or substances. VEGF-C is a representative member of the VEGF family; it binds to its cognate receptor VEGFR-3 and stimulates lymphangiogenesis and the new growth of lymphatic vessels. VEGFR-3 expression in Hca-F cells was decreased by Ups-fucoidan treatment.
This discovery indicates that HGF/MET and VEGF-C/VEGFR-3 dual signaling pathways may be why Hca-F cell lines have high lymphatic metastasis potential. Also, in this study, VEGF-C/VEGFR-3, HGF/c-MET, pPI3K, p-Akt, p-ERK1/2, and NF-kB down-regulated in cells treated with Ups-fucoidan. This result indicates that Ups-fucoidan inhibits tumor growth and metastasis by inactivating relevant signaling pathways
The findings indicate that Ups-fucoidan may inhibit tumor metastasis, so it is believed that Fucoidan will be applied as a therapeutic agent for metastatic Liver cancer.
Souce: PLoS One. 2014; 9(8): e106071 doi: 10.1371/journal.pone.0106071