Michael G. Johnson

ABSTRACT: We studied the effectiveness of partial replacement of glycerol with citric, lactic, malic, and tartaric acids on the antimicrobial activities of nisin (205 IU/g protein)‐incorporated soy protein film against Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella gaminara. S. gaminara inoculated into 2.6% malic acid‐incorporated films and lactic acid‐incorporated films with nisin (5.7 and 3.4 log number colony‐forming units (CFU)/mL, respectively) and without nisin (3.2 and 3.0 log number CFU/mL, respectively) had fewer survivors than HCl‐incorporated film with and without nisin (8.6 and 7.9 log number CFU/mL, respectively). Malic acid (2.6%)‐incorporated soy protein film had the fewest survivors of L. monocytogenes, S. gaminara , and E. coli O157:H7 (5.5, 3.0, and 6.8 log number CFU/mL, respectively) and has the potential to inhibit a wide spectrum of microbes in product application.

Tumor cells aberrantly express chemokines and/or chemokine receptors, and some may promote tumor growth and metastasis. We examined the expression and function of chemokine receptor CXCR3 in a syngeneic murine model of metastatic breast cancer. By flow cytometry, CXCR3 was detected in all murine mammary tumor cell lines examined. All human breast cancer cell lines examined also expressed CXCR3, as did the immortalized but nontumorigenic MCF-10A cell line. Interaction of CXCR3 ligands, CXCL9, CXCL10, and CXCL11, with CXCR3 on the highly malignant murine mammary tumor cell line 66.1 resulted in intracellular calcium mobilization and chemotaxis in vitro. To test the hypothesis that tumor metastasis is facilitated by CXCR3 expressed by tumor cells, we employed a small molecular weight antagonist of CXCR3, AMG487. 66.1 tumor cells were pretreated with AMG487 prior to i.v. injection into immune-competent female mice. Antagonism of CXCR3 on 66.1 tumor cells inhibited experimental lung metastasis, and this antimetastatic activity was compromised in mice depleted of natural killer cells. Systemic administration of AMG487 also inhibited experimental lung metastasis. In contrast to the antimetastatic effect of AMG487, local growth of 66.1 mammary tumors was not affected by receptor antagonism. These studies indicate that murine mammary tumor cells express CXCR3 which facilitates the development of lung metastases. These studies also indicate for the first time that a small molecular weight antagonist of CXCR3 has the potential to inhibit tumor metastasis.