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  • 1
    ISSN: 1573-7217
    Keywords: stromal epithelial interactions ; insuline-like growth factors ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prominent ‘desmoplastic’ or stromal reaction seen in many invasive breast carcinomas lead to early speculation that stromal cells play a role in breast cancer pathogenesis [1]. Experimental evidence now supports this hypothesis and interactions between stromal cells and epithelial cells appear to be important for both normal mammary development and neoplasia. The identification of genes that are selectively expressed in the stroma of malignant breast lesions has recently provided new insights into the molecular basis of stromal-epithelial interactions. Stromally expressed genes include growth factors, proteases and extracellular matrix proteins, all biological activities with potential roles in malignant progression. Investigations discussed here concern the nature of the paracrine signals provided by malignant epithelial cells that activate changes in stromal gene expression, the effect that the stromally derived factors have on the behavior of malignant epithelial cells and the identification of novel factors and receptors in either stroma or epithelia that contribute to their mutual interactions. These questions will be addressed in the context of this laboratory's studies on insulin-like growth factors, as these molecules show marked differences in stromal expression between benign and malignant breast tissue and thus provide a useful paradigm for investigations into the paracrine environment of an evolving breast tumor.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 22 (1992), S. 21-29 
    ISSN: 1573-7217
    Keywords: autocrine growth factors ; hormone dependence ; IGF-I ; IGF-II ; paracrine growth factors ; stromal cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The insulin-like growth factors (IGFs) are mitogens for many cancer cell types. In breast cancer cells, IGF-I and IGF-II have both been shown to stimulate cell proliferation. However, IGF-I mRNA has not been found in human breast cancer cell lines, making it unlikely that IGF-I is commonly expressed as an autocrine growth factor for breast cancer cells. Nevertheless, IGF-I mRNA can be detected in breast cancer tissue samples, and in situ hybridization studies have shown that the message originates from the stromal cells adjacent to normal lobules. IGF-II, on the other hand, has been detected in some breast cancer cell lines. In the estrogen receptor positive cell line T47-D, IGF-II mRNA was induced by estradiol. Furthermore, transfection of an IGF-II expression vector into a previously estrogen-dependent cell line resulted in hormone independent growth. Thus, IGF-II can be expressed as an autocrine growth factor in some breast cancers and its expression may, in part, result in hormone independence. Finally, stromal cells obtained from breast tissues showed that IGF-I was commonly expressed in fibroblasts derived from non-malignant biopsy specimens, while IGF-II mRNA was detected in fibroblasts adjacent to malignant tissue. These studies suggest that IGF-II expression may be important in both autocrine and paracrine regulation of breast cancer cell growth.
    Type of Medium: Electronic Resource
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