Dietary intake of a plant phospholipid/lipid conjugate reduces lung cancer growth and tumor angiogenesis.

It is well recognized that early detection and cancer prevention are significant armaments in the 'war against cancer'. Changes in lifestyle and diet have significant impact on the global incidence of cancer. For over 30 years, many investigators have studied the concept of chemoprevention. More recently, with the demonstration that antiangiogenic activity reduces tumor growth, the concept of angioprevention has emerged as a novel strategy in the deterrence of cancer development (carcinogenesis). In this study, we utilized a fast growing, highly aggressive murine Lewis lung cancer model to examine the in vivo antitumor effects of a novel, dietary supplement, known as plant phospholipid/lipid conjugate (pPLC). Our goal was to determine if pPLC possessed direct antitumor activity with relatively little toxicity that could be developed as a chemoprevention therapy. We used pPLC directly in this in vivo model due to the lack of aqueous solubility of this novel formulation, which precludes in vitro experimentation. pPLC contains known antioxidants, ferulic acid and lipoic acid, as well as soy sterols, formulated in a unique aqueous-insoluble matrix. The pPLC dietary supplement was shown to suppress in vivo growth of this tumor model by 30%. We also demonstrated a significant decrease in tumor angiogenesis accompanied by increased apoptosis and present preliminary evidence of enhanced expression of the hypoxia-related genes pentraxin-3 and metallothionein-3, by 24.9-fold and 10.9-fold, respectively, compared with vehicle control. These findings lead us to propose using this plant phosolipid/lipid conjugate as a dietary supplement that may be useful in cancer prevention.

Influence of Stromal Components on Lung Cancer Carcinogenesis.

The association between tumor growth and angiogenesis was first observed over 100 years ago. Since then, research has shown the dependence of tumor growth on angiogenesis and the ability of cancer cells to alter the stromal microenvironment. Technological advancements have enabled researchers to identify cell types within a tumor, identify chemokines, cytokines, and growth factors secreted by tumor cells, show the interaction between tumor cells and stroma, and investigate the function of distinct genes using knockout and transgenic mouse technology. This review provides an overview of tumor growth, emphasizing research using in vivo mouse models on vascular endothelial growth factor (VEGF), fibrinogen, fibronectin, plasminogen, and MMPs in primary tumor growth and metastasis of lung cancer in particular.

Matrix metalloproteinases: changing roles in tumor progression and metastasis.

Articles on tumor invasion, metastasis, and angiogenesis in normal and disease states have been well represented among the pages of The American Journal of Pathology. In addition to exciting interest in a variety of disease processes, these studies have been central in defining the emerging field in cancer research known as the tumor microenvironment. Early studies in this field established the importance of the extracellular matrix on tumor cell growth and differentiation. With time, the role of the extracellular matrix and matrix metalloproteinases in the regulation of tumor invasion, metastasis, and angiogenesis was recognized, and AJP has published seminal articles in this field. Moreover, recent studies show evidence for a role of matrix metalloproteinases in the regulation of inflammation within tumor lesions, making the targeting of matrix metalloproteinases in cancer therapy even more complex. This review attempts to summarize the contribution of AJP to some of the key changes that have led to the evolution of this field.