Multi‐faceted regulation of cell differentiation by extracellular matrix

Extracellular matrix (ECM) is an intricate network composed of an array of macromolecules, the importance of which is becoming increasingly apparent. The ECM is an integral part of the machinery that regulates cell function; its role in cell differentiation and tissue‐specific gene expression, although essential, is not yet understood. It can act as a positive as well as a negative regulator of functional differentiation depending on the cell type and the genes studied. It also acts in a hierarchical fashion, exacting higher and higher degrees of stringency to achieve full functional differentiation. Regulation by ECM is closely interrelated with the action of other regulators of cellular function, such as growth factors and hormones. But ECM may exert its regulation of gene expression by mechanisms distinct from those known for soluble transcription factors. In this short review, we describe three systems in which ECM has been shown to play a crucial role in functional differentiation, but we emphasize mainly the work from our own laboratory to provide a more in‐depth analysis of one system. The three systems are: mouse mammary epithelial cells, rat hepatocytes, and human keratinocytes. The crucial role of ECM in normal cell differentiation implies that its alteration may have serious consequences in malignancies and other diseases. The current functional cell culture models could provide powerful tools not only for understanding regulation of normal cell function but also for the studies of tumorigenesis and possibly cancer therapy.—Lin, C. Q., Bissell, M.J. Multi‐faceted regulation of cell differentiation by extracellular matrix. FASEB J. 7: 737‐743; 1993.

[1]  H. Green,et al.  Seria cultivation of strains of human epidemal keratinocytes: the formation keratinizin colonies from single cell is , 1975, Cell.

[2]  Josephine C. Adams,et al.  Changes in keratinocyte adhesion during terminal differentiation: Reduction in fibronectin binding precedes α 5 β 1 integrin loss from the cell surface , 1990, Cell.

[3]  B. Groner,et al.  Prolactin and glucocorticoid hormones synergistically induce expression of transfected rat beta-casein gene promoter constructs in a mammary epithelial cell line. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Z. Werb,et al.  Signal transduction by integrin receptors for extracellular matrix: Cooperative processing of extracellular information , 1992, Current Biology.

[5]  AC Tose.  Cell , 1993, Cell.

[6]  M. Bissell,et al.  A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression. , 1992, Molecular biology of the cell.

[7]  T. Nakamura,et al.  Glucocorticoid-dependent expression of the albumin gene in adult rat hepatocytes. , 1986, The Journal of biological chemistry.

[8]  J. Maher,et al.  Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver. , 1987, The Journal of clinical investigation.

[9]  A. Ben-Ze'ev,et al.  Cell-cell and cell-matrix interactions differentially regulate the expression of hepatic and cytoskeletal genes in primary cultures of rat hepatocytes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[11]  F. Watt,et al.  Changes in the abundance and distribution of actin and associated proteins during terminal differentiation of human epidermal keratinocytes. , 1991, Journal of cell science.

[12]  H Green,et al.  Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. , 1975, Cell.

[13]  M J Bissell,et al.  How does the extracellular matrix direct gene expression? , 1982, Journal of theoretical biology.

[14]  S. Nandi,et al.  Hormonal effects on intracellular and secreted casein in cultures of mouse mammary epithelial cells on floating collagen membranes. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Jackson,et al.  Conditional enhancement of liver-specific gene transcription. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Caron,et al.  Induction of albumin gene transcription in hepatocytes by extracellular matrix proteins , 1990, Molecular and cellular biology.

[17]  M. Bissell,et al.  Expression of extracellular matrix components is regulated by substratum , 1990, The Journal of cell biology.

[18]  M. Bissell,et al.  Dynamic reciprocity: how do extracellular matrix and hormones direct gene expression? , 1987, Progress in clinical and biological research.

[19]  M. Bissell,et al.  Designer microenvironments for the analysis of cell and tissue function. , 1990, Current opinion in cell biology.

[20]  G. Michalopoulos,et al.  Cytochrome P-450 induction by phenobarbital and 3-methylcholanthrene in primary cultures of hepatocytes. , 1976, Science.

[21]  F. Watt.  Selective migration of terminally differentiating cells from the basal layer of cultured human epidermis , 1984, The Journal of cell biology.

[22]  R L Juliano,et al.  Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[23]  P. Chambon,et al.  A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas , 1990, Nature.

[24]  T. Dale,et al.  High-level expression of the rat whey acidic protein gene is mediated by elements in the promoter and 3' untranslated region , 1992, Molecular and cellular biology.

[25]  L. Hennighausen,et al.  Expression of a whey acidic protein transgene during mammary development. Evidence for different mechanisms of regulation during pregnancy and lactation. , 1991, The Journal of biological chemistry.

[26]  M. Bissell,et al.  Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity , 1991, The Journal of cell biology.

[27]  J. Rosen,et al.  Transcriptional Analysis of the Mouse β-Casein Gene , 1990, Molecular endocrinology.

[28]  Bissell Dm.  Study of hepatocyte function in cell culture. , 1976 .

[29]  Lawrence,et al.  A novel regulatory mechanism for whey acidic protein gene expression. , 1989, Cell regulation.

[30]  M. Bissell,et al.  The Significance of the Extracellular Matrix in Mammary Epithelial Carcinogenesis , 1993 .

[31]  J. Rosen,et al.  Tissue-specific, high level expression of the rat whey acidic protein gene in transgenic mice. , 1990, Nucleic acids research.

[32]  F. Watt,et al.  An unusual strain of human keratinocytes which do not stratify or undergo terminal differentiation in culture , 1988, The Journal of cell biology.

[33]  L E Babiss,et al.  Transcriptional regulation of the albumin gene in cultured rat hepatocytes. Role of basement-membrane matrix. , 1990, Molecular biology & medicine.

[34]  P. Guzelian,et al.  PHENOTYPIC STABILITY OF ADULT RAT HEPATOCYTES IN PRIMARY MONOLAYER CULTURE * , 1980, Annals of the New York Academy of Sciences.

[35]  D. Bissell.  Study of hepatocyte function in cell culture. , 1976, Progress in liver diseases.

[36]  L. Liotta,et al.  Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. , 1982, Biochemistry.

[37]  Josephine C. Adams,et al.  Fibronectin inhibits the terminal differentiation of human keratinocytes , 1989, Nature.

[38]  F. Watt,et al.  Cell shape controls terminal differentiation of human epidermal keratinocytes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[39]  M. Bissell,et al.  Extracellular matrix and hormones transcriptionally regulate bovine beta-casein 5' sequences in stably transfected mouse mammary cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[40]  C. DiPersio,et al.  Extracellular signals that regulate liver transcription factors during hepatic differentiation in vitro , 1991, Molecular and cellular biology.

[41]  D. Medina,et al.  Epithelial mouse mammary cell line exhibiting normal morphogenesis in vivo and functional differentiation in vitro. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[42]  B. Groner,et al.  Developmental and environmental regulation of a mammary gland-specific nuclear factor essential for transcription of the gene encoding beta-casein. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[43]  J. Darnell,et al.  Changes in liver-specific compared to common gene transcription during primary culture of mouse hepatocytes , 1983, Molecular and cellular biology.