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Suppression of cancer metastasis

Inactive Publication Date: 2012-12-06
ACAD SINIC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]In some embodiments of the invention compositions of fibrillar proteins as anti-cancer metastasis therapeutics are provided, where the composition provides for a pharmaceutical formulation in a dose effective to inhibit metastasis. In another aspect, the invention relates to a method comprising manufacturing a composition for use in treating a patient having cancer. The method comprises manufacturing fibrillar human serum albumin, and mixing the fibrillar human serum albumin with a pharmaceutically acceptable carrier. In another aspect, the invention relates to a method comprising dissolving HSA in an SDS solution; applying the dissolved HSA through a gel filtration column with a pore size to separate proteins of 70 kDa molecular weight and above; eluting the HSA from the column; and dialyzing the solution against phosphate buffered saline to remove the SDS.

Problems solved by technology

Cancer metastasis is the most common cause of treatment failure and death in cancer patients.

Method used

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  • Suppression of cancer metastasis
  • Suppression of cancer metastasis
  • Suppression of cancer metastasis

Examples

Experimental program
Comparison scheme
Effect test

example 1

Methods

[0157]Cell Lines and Culture.

[0158]SK-OV-3 cells (human ovarian carcinoma cell line; ATCC HTB-77) and SK-OV-3ip.1 cells, and CaSki cells (human cervical carcinoma cell line; ATCC CRL-1550) were maintained at 37° C. in McCoy's 5A and RPMI-1640 medium, respectively. MDA-MB-231 cells (human mammary adenocarcinoma cell line; ATCC HTB-26) and TS / A cells (murine mammary adenocarcinoma cell line) were maintained at 37° C. in Dulbecco's modified Eagle's medium (DMEM) / F12 medium and DMEM, respectively. PC-3 cells (human prostate adenocarcinoma cell line; ATCC CRL-1435) and 22Rv1 cells (human prostate carcinoma cell line; ATCC CRL-2505) were maintained at 37° C. in RPMI-1640 medium. All medium were supplemented with 10% fetal bovine serum (FBS), 2 mM L-glutamine, 100 units / ml penicillin, and 100 μg / ml streptomycin.

[0159]Cytotoxicity Assay.

[0160]Cell survival was determined by MTT assay or WST-1 assay. In brief, 1×105 cells / well of tumor cells were seeded in 96-well plates in serum-free...

example 2

rVP1 Suppressed Tumor Cell Metastasis In Vivo

[0181]A. In Vitro rVP1-Treated MDA-MB-231 Cells Followed by i.v. Injection into BALB / C Mice.

[0182]We then examined whether pretreated MDA-MB-231 human mammary adenocarcinoma cells with rVP1 for 24 h to inhibit metastatic ability in vitro then injected the cells intravenously in mice could reduce their metastasis in mice lung as compare with MDA-MB-231 cells without rVP1 pretreatment. Data showed that 0.1 and 0.2 μM rVP1-treated MDA-MB-231 cells significantly decreased cancer cells metastasis in mice lung tissue (FIG. 4A). The related lung weight and the number of tumor foci in lung were also significantly decrease compared to tumor group without rVP1 treatment (FIGS. 4B-C).

[0183]B. Orthotropic PC-3 Xenograft Model.

[0184]We also examined whether rVP1 could suppress prostate cancer metastasis in vivo. PC-3 human prostate adenocarcinoma cells were first orthotopically implanted to nude mice' prostate and 4-wks or 10-wks after implantation, r...

example 3

F-HSA Suppressed Tumor Cell Invasion and / or Migration in MDA-MB-231 Cells, PC-3 Cells, 22Rv1 Cells and CaSki Cells In Vitro

[0187]To examine whether other fibrillar proteins such as F-HSA also suppressed cancer cell invasion and / or migration, the effect of F-HSA on cancer cell invasion and / or migration were measured by using Boyden chamber assay. After being treated with various concentrations of F-HSA (0.1 μM to 0.2 μM F-HSA in MDA-MB-231 cells; 0.025 to 0.1 μM F-HSA in PC-3 cells; 0.025 to 0.05μM F-HSA in 22Rv1 cells; 0.2 to 0.4 μM F-HSA in CaSki cells), the invasion and / or migration abilities of a variety of cancer cells were significantly suppressed. It is of note that at these concentrations, F-HSA did not affect cell viability by using MTT assay (FIG. 7).

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Abstract

Methods are provided for suppressing cancer metastasis. Cancer metastasis is the most common cause of treatment failure and death in cancer patients. Tumor cell invasion and / or migration can be significantly inhibited after fibrillar proteins (rVP1, F-HSA, and F-BSA) treatment in vitro. In addition, rVP1 can significantly suppress murine and human breast cancer metastasis and human prostate and ovarian cancer metastasis in vivo while F-HSA can significantly suppress murine breast cancer metastasis. Compositions of fibrillar proteins as anti-cancer metastasis therapeutics and methods of use thereof are provided herein.

Description

INTRODUCTION[0001]Cancer metastasis is a process that involves a series of sequential steps and requires a cascade of host-tumor cell interactions (Steeg P S et al. (2007) Nature 449:671-3). These steps include detachment from the primary tumor, invasion into and arrest in circulatory systems, extravasation into the parenchyma of organs; and proliferation in association with angiogenesis (Sawyer T K et al. (2004) Expert Opin Investig Drugs 13:1-19). There are growing interests in investigating the mechanisms of migration and invasion, which are unveiled to be a critical step of the metastatic process. Interference at any one of these steps to block the metastatic cascade represents an attractive approach to prevent the formation of metastatic tumor growths.[0002]Our previous data showed that recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus (FMDV), induced apoptosis in several kinds of cancer cells via integrin signaling pathway (Peng J M et al. (2004) J. Biol. C...

Claims

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Application Information

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IPC IPC(8): A61K38/38A61P35/04A61K38/16
CPCA61K38/385A61K38/38A61K38/162C07K14/765A61K47/643A61P35/00A61P35/04A61K47/50A61K38/00A61K38/17C07K14/76A61K45/06A61N5/10C12N7/00C12N2770/32133
Inventor LIANG, SHU-MEICHIU, CHING-FENGHUNG, SHAO-WENPENG, JEI-MINGLIANG
Owner ACAD SINIC
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