Inhibitory activity of YKL-40 in mammary epithelial cell differentiation and polarization induced by lactogenic hormones: a role in mammary tissue involution

Autor: Brooke Bentley, Qing Jackie Cao, Rong Shao, Steve Scully, Wei Yan
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Anatomy and Physiology
Hydrocortisone
Angiogenesis
Cellular differentiation
Glycobiology
Gene Expression
lcsh:Medicine
Biochemistry
0302 clinical medicine
Cell Movement
Lectins
Molecular Cell Biology
Breast Tumors
Insulin
lcsh:Science
Epithelial cell differentiation
0303 health sciences
Multidisciplinary
Caseins
Cell Polarity
Cell Differentiation
Cadherins
3. Good health
Cell biology
Drug Combinations
Milk
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Medicine
Female
Proteoglycans
Collagen
Research Article
musculoskeletal diseases
medicine.medical_specialty
Histology
Morphogenesis
Biology
Cell Line
03 medical and health sciences
Mammary Glands
Animal
Adipokines
Internal medicine
Genetics
Cancer Genetics
medicine
Animals
Humans
Lactation
Involution (medicine)
Chitinase-3-Like Protein 1
Glycoproteins
030304 developmental biology
Matrigel
lcsh:R
Cancers and Neoplasms
Epithelial Cells
Hormones
Epithelium
Prolactin
Endocrinology
Cell culture
lcsh:Q
Laminin
Biomarkers
Developmental Biology
Zdroj: PLoS ONE, Vol 6, Iss 10, p e25819 (2011)
PLoS ONE
ISSN: 1932-6203
Popis: We previously reported that a secreted glycoprotein YKL-40 acts as an angiogenic factor to promote breast cancer angiogenesis. However, its functional role in normal mammary gland development is poorly understood. Here we investigated its biophysiological activity in mammary epithelial development and mammary tissue morphogenesis. YKL-40 was expressed exclusively by ductal epithelial cells of parous and non-parous mammary tissue, but was dramatically up-regulated at the beginning of involution. To mimic ductal development and explore activity of elevated YKL-40 during mammary tissue regression in vivo, we grew a mammary epithelial cell line 76N MECs in a 3-D Matrigel system in the presence of lactogenic hormones including prolactin, hydrocortisone, and insulin. Treatment of 76N MECs with recombinant YKL-40 significantly inhibited acinar formation, luminal polarization, and secretion. YKL-40 also suppressed expression of E-cadherin but increased MMP-9 and cell motility, the crucial mechanisms that mediate mammary tissue remodeling during involution. In addition, engineering of 76N MECs with YKL-40 gene to express ectopic YKL-40 recapitulated the same activities as recombinant YKL-40 in the inhibition of cell differentiation. These results suggest that YKL-40-mediated inhibition of cell differentiation and polarization in the presence of lactogenic hormones may represent its important function during mammary tissue involution. Identification of this biophysiological property will enhance our understanding of its pathologic role in the later stage of breast cancer that is developed from poorly differentiated and highly invasive cells.
Databáze: OpenAIRE
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