"Our breakthrough findings demonstrate that PTN-activated stromal cells are responsible for the ultimate remodelling of extracellular matrix proteins, as well as the release of factors that stimulate the growth of malignant cancer cells," Deuel said.
"We've shown that PTN secreted from breast cancer cells is the key mechanism of stromal cell activation, and that PTN alone is sufficient to stimulate many of the critical signalling pathways that aggressively promote breast cancer progression."
Using genetically modified mouse models, the study found that the inappropriate expression of PTN produced breast cancers of a more aggressive subtype. In those same mouse models, highly malignant cells of scirrhous carcinoma-a hard, fibrous tumour-were found to express very high levels of the mouse mammary tumour virus (MMTV)-Ptn transgene along with increases in collagen, elastin, tumour angiogenesis, and increased size of new blood vessels within the breast cancers-all markers for breast cancer.
"Our study suggests the possibility that PTN expression may account for many of the features of scirrhous carcinoma seen in the breast cancers of these mice," Deuel said.
"Pleiotrophin stimulates new collagen of different subtypes and new elastin synthesis. Collagen fragments are known to stimulate growth of carcinoma cells and to stimulate anti-apoptotic pathways, favouring growth of the carcinoma cells," he added.
Other authors of the study, Secretion of Pleiotrophin Stimulates Breast Cancer Progression Through Remodeling of the Tumor Microenvironment, include Yunchao Chang, Masahiko Zuka, and Pablo Perez-Pinera of The Scripps Research Institute; Aurora Astudillo of the Hospital Universitario Central de Asturias, Oviedo, Spain; Joanne Mortimer of the University of California San Diego; and James R. Berenson of the Institute for Myeloma and Bone Cancer Research, Los Angeles.
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