Neurokinin Receptors and Subtypes as Potential Targets in Breast Cancer: Relevance to Bone Marrow Metastasis

Authors: A. Moharita; J. S. Harrison; P. Rameshwar

Source: Drug Design Reviews - Online, Volume 1, Number 4, October 2004 , pp. 297-302(6)

Publisher: Bentham Science Publishers

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Abstract:

Despite improved treatments and early detection of breast cancer (BC), bone metastasis remains a clinical dilemma. The time interval between breast cancer cell (BCC) entry in the bone marrow (BM) and clinically apparent bone metastasis could be years, suggesting that the marrow might allow for quiescence of BCCs. This review discusses the molecular mechanism by which BCCs enter and integrate into the BM microenvironment long before the cancer is clinically detected. BCCs entering the BM can be subdivided based on the cells' locations within the BM: I) BCCs within the stromal compartment and close to the endosteum are defined as cells undergoing epithelial to mesenchymal to stromal transition (EMST), and II) Rapidly proliferating BCCs located within the central medullary region. The preprotachykinin- I (PPT-I) gene and genes for cognate receptors, neurokinin-1 subtypes (full-length and truncated) and NK-2, are linked to BC development, including early entry into the BM. NK receptors form a network with cytokines and other molecules to promote the survival and quiescence of BCCs. A central role of NK receptors in the early entry of BCC into the BM microenvironment is discussed. We propose that NK receptors and subtypes are potential targets for breast, and perhaps other endocrine-linked cancers, during different phases of the disease.

Keywords: breast cancer; bone marrow; neurokinin receptors; tachykinins; invasion

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567269043390771

Affiliations: 1: UMDNJ-New Jersey Medical School; MSB; Rm. E-579, 185 South Orange Ave; Newark.

Publication date: 2004-10-01