The multifaceted role of periostin in tumorigenesis

Periostin, also called osteoblast-specific factor 2 (OSF-2), is a member of the fasciclin family and a disulfide-linked cell adhesion protein that has been shown to be expressed preferentially in the periosteum and periodontal ligaments, where it acts as a critical regulator of bone and tooth formation and maintenance. Furthermore, periostin plays an important role in cardiac development. Recent clinical evidence has also revealed that periostin is involved in the development of various tumors, such as breast, lung, colon, pancreatic, and ovarian cancers. Periostin interacts with multiple cell-surface receptors, most notably integrins, and signals mainly via the PI3-K/Akt and other pathways to promote cancer cell survival, epithelial–mesenchymal transition (EMT), invasion, and metastasis. In this review, aspects related to the function of periostin in tumorigenesis are summarized.     

The role of periostin in tissue remodeling across health and disease

Periostin, also termed osteoblast-specific factor 2, is a matricellular protein with known functions in osteology, tissue repair, oncology, cardiovascular and respiratory systems, and in various inflammatory settings. However, most of the research to date has been conducted in divergent and circumscribed areas meaning that the overall understanding of this intriguing molecule remains fragmented. Here, we integrate the available evidence on periostin expression, its normal role in development, and whether it plays a similar function during pathologic repair, regeneration, and disease in order to bring together the different research fields in which periostin investigations are ongoing. In spite of the seemingly disparate roles of periostin in health and disease, tissue remodeling as a response to insult/injury is emerging as a common functional denominator of this matricellular molecule. Periostin is transiently upregulated during cell fate changes, either physiologic or pathologic. Combining observations from various conditions, a common pattern of events can be suggested, including periostin localization during development, insult and injury, epithelial–mesenchymal transition, extracellular matrix restructuring, and remodeling. We propose mesenchymal remodeling as an overarching role for the matricellular protein periostin, across physiology and disease. Periostin may be seen as an important structural mediator, balancing appropriate versus inappropriate tissue adaption in response to insult/injury.     

The multifaceted role of glial cells in amyotrophic lateral sclerosis

Despite indisputable progress in the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a mechanistic comprehension of the neurodegenerative processes typical of this disorder is still missing and no effective cures to halt the progression of this pathology have yet been developed. Therefore, it seems that a substantial improvement of the outcome of ALS treatments may depend on a better understanding of the molecular mechanisms underlying neuronal pathology and survival as well as on the establishment of novel etiological therapeutic strategies. Noteworthy, a convergence of recent data from multiple studies suggests that, in cellular and animal models of ALS, a complex pathological interplay subsists between motor neurons and their non-neuronal neighbours, particularly glial cells. These observations not only have drawn attention to the physiopathological changes glial cells undergo during ALS progression, but they have moved the focus of the investigations from intrinsic defects and weakening of motor neurons to glia–neuron interactions. In this review, we summarize the growing body of evidence supporting the concept that different glial populations are critically involved in the dreadful chain of events leading to motor neuron sufferance and death in various forms of ALS. The outlined observations strongly suggest that glial cells can be the targets for novel therapeutic interventions in ALS.     

Inhibitor of growth tumor suppressors in cancer progression

The inhibitor of growth (ING) family of tumor suppressors has five members and is implicated in the control of apoptosis, senescence, DNA repair, and cancer progression. However, little is known about ING activity in the regulation of cancer progression. ING members and splice variants seem to behave differently with respect to cancer invasion and metastasis. Interaction with histone trimethylated at lysine 4 (H3K4me3), hypoxia inducible factor-1 (HIF-1), p53, and nuclear factor kappa-B (NF-κB) are potential mechanisms by which ING members exert effects on invasion and metastasis. Subcellular mislocalization, rapid protein degradation, and to a lesser extent ING gene mutation are among the mechanisms responsible for inappropriate ING levels in cancer cells. The aim of this review is to summarize the different roles of ING family tumor suppressors in cancer progression and the molecular mechanisms involved.     

The role of nucleic acids in crown-gall tumor induction

Zusammenfassung Die Arbeit befasst sich mit der Induzierung von Pflanzentumoren durch dasAgrobacterium tumefaciens. Es konnte nachgewiesen werden, dass die Nukleinsäurefraktion aus dem Bacterium imstande ist, nach Zugabe zu einem Homogenisat von verletztenDatura-stramonium-Pflanzen ein Tumor auslösendes Prinzip aufzubauen. Eine derartige (sterile) Fraktion ist in der Lage, echte Crown-Gall-Tumoren zu induzieren, deren Identität mit den bakteriell erzeugten Tumoren morphologisch, histologisch und physiologisch erwiesen ist.     

Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cell

More than 10 years have passed since the naming of periostin derived from its expression sites in the periosteum and periodontal ligament. Following this finding, we have accumulated more data on the expression patterns of periostin, and, finally, with the generation of periostin-deficient mice, have revealed functions of periostin in the regeneration of tissues in bone, tooth, heart, and skin, and its action in cancer invasion. Since periostin is a matricellular protein, the first investigation of periostin function showed its enhancement of cell migration by acting outside the cell. On the other hand, recent observations have demonstrated that periostin functions in fibrillogenesis in association with extracellular matrix molecules inside the cell.     

The urokinase receptor and integrins in cancer progression

Enhanced levels of expression of urokinase receptor (uPAR) and certain integrins have been linked to cancer cell progression. This has classically been attributed to matrix degradation via the activation of the urokinase (uPA)/plasmin system and modulation of cell motility and survival through integrin engagement. More recently, uPAR has been shown to play multiple roles independent of protease activity. Specifically, uPAR has been shown to be intimately involved in the regulation of cell adhesion, migration and proliferation in part through interactions with other membrane partners, including integrins. The goal of this review is to summarize recent insights in the function of uPAR/integrin interactions, to provide a framework for understanding the importance of these interactions in the context of cancer, and to highlight its potential as a target for therapeutic intervention.     

The emerging role for sphingolipids in the eukaryotic heat shock response

Eukaryotic cells have a highly conserved response to an increase in temperature, termed the heat shock response. Recent research has revealed multiple roles for various sphingolipids in the heat shock responses of both yeast and mammalian cells. Heat stressed or shocked yeast and mammalian cells have an acute activation of serine palmitoyltransferase, resulting in the de novo biosynthesis of sphingolipids. Also, both mammalian and yeast cells were shown to increase ceramide levels upon heat stress or shock. In yeast cells, several functions have emerged for the de novo produced sphingoid bases in terms of the heat stress response. These functions include a role in accumulation of trehalose, a role in the heat-induced transient G0/G1 cell cycle arrest and phytosphingosine activation of a ubiquitin protein degradation pathway. However, in mammalian systems, ceramides have been demonstrated as bioactive lipids. Ceramides produced in response to heat shock were demonstrated to induce the production of c-jun, leading to apoptosis, and to be upstream of dephosphorylation of serine-rich proteins. Increasingly, sphingolipids are emerging as bioactive signaling molecules involved in numerous aspects of the eukaryotic heat shock response.     

The role of crustecdysone in the moulting crayfish

Résumé La crustecdysone injectée dans l'écrevisse,Procambarus sinulans ne cause pas la mue chez l'animal intact mais l'accélère après ablation des pédoncules oculaires.     

The role of the thymus in antinuclear autoimmunization

Résumé La thymectomie chez des souris CF1 âgées de 1 mois est suivie comme dans le cas de la thymectomie néonatale de l'apparition d'anticorps antinucléaires. Le transfert adoptif de l'autoimmunité antinucléaire apparu chez des animaux thymectomisés à la naissance n'est possible que si les animaux receveurs sont eux-mêmes thymectomisés. Ces constatations mettent en évidence un rôle possible de contrôle des réactions autoimmunes par le thymus.     

A gelatin sponge model for studying tumor growth: quantitation of tumor cells and leukocytes in the CHO tumor

Summary A gelatin sponge model system for tumor cell inoculation and retrieval of tumor-associated leukocytes is described. Gelatin sponges pre-implanted in nude mice harboring tumorigenic Chinese hamster ovary cells (line CHO) were examined at 2 and 11 days after injection of tumor cells for tumor cell content and leukocyte accumulation after digesting the sponge matrix in collagenase solution.The data indicate a progressive influx of host cells consisting primarily of macrophages, neutrophils and lymphocytes. The total number of viable tumor cells as well as the fraction of surviving tumor cells with clonogenic potential also increased with tumor age. Blank sponges not harboring tumor cells elicited an inflammatory response in the animals which did not change appreciably with length of sponge residence. However, when the sponges were harboring tumor cells, the accumulation of host leukocytes far exceeded that which occurred in blank sponges. This observation suggests a host response directed toward the tumor which is absent in animals bearing blank sponges. Apart from providing anchorage for injected cells, the gelatin sponge, by virtue of its digestibility in collagenase, makes possible the easy retrieval and precise quantitation of tumor-associated host cells.Supported by the United States Department of Energy and National Institutes of Health Grant P41-RR01315.     

A gelatin sponge model for studying tumor growth: quantitation of tumor cells and leukocytes in the CHO tumor

A gelatin sponge model system for tumor cell inoculation and retrieval of tumor-associated leukocytes is described. Gelatin sponges pre-implanted in nude mice harboring tumorigenic Chinese hamster ovary cells (line CHO) were examined at 2 and 11 days after injection of tumor cells for tumor cell content and leukocyte accumulation after digesting the sponge matrix in collagenase solution. The data indicate a progressive influx of host cells consisting primarily of macrophages, neutrophils and lymphocytes. The total number of viable tumor cells as well as the fraction of surviving tumor cells with clonogenic potential also increased with tumor age. Blank sponges not harboring tumor cells elicited an inflammatory response in the animals which did not change appreciably with length of sponge residence. However, when the sponges were harboring tumor cells, the accumulation of host leukocytes far exceeded that which occurred in blank sponges. This observation suggests a host response directed toward the tumor which is absent in animals bearing blank sponges. Apart from providing anchorage for injected cells, the gelatin sponge, by virtue of its digestibility in collagenase, makes possible the easy retrieval and precise quantitation of tumor-associated host cells.     

The role of glycine in the biosynthesis of steroids

Zusammenfassung Während der Biosynthese von Cholesterol mit homogenisierter Rattenleber wird [2-¹⁴C] des Glycins viel besser eingebaut als [1-¹⁴C].Saccharomyces cerevisiae produziert radioaktives Squelen (ausser Ergosterol mit Radioaktivität des Ringsystems) mit [2-¹⁴C] Glycin und mit [3-¹⁴C] Serin, aber nicht mit [1-¹⁴C] Glycin.

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Studies on Biosynthesis. Part VI. For Part V, seeA. K. Bose, K. S. Khanchandani andB. L. Hungund, Experientia,27, 1403 (1971). b) Presented at the 164th National Meeting of the American Chemical Society, New York, August, 1972.

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The support of this research by Stevens Institute of Technology and Sandoz Foundation is gratefully acknowledged. We wish to thank Drs.P. T. Funke, M. S. Manhas, P. K. Bhattacharyya, M. Anchel andH. Levey for valuable discussions and help with some of the experiments.