The role of periostin in neoplastic processes

Periostin, also called osteoblast-specific factor 2 (OSF-2), is a multifunctional glycoprotein that belongs to the group of matricellular proteins. Due to its characteristic molecular structure containing integrin-binding domains, periostin is capable of binding to multiple integrin receptors (αvβ3, αvβ5, α6β4), thus affecting the regulation of the intracellular signaling pathways associated with protein kinases PI3K/AKT and focal adhesion kinase (FAK). This protein thus plays a role in the adhesion process, in the migration of many cells, and importantly, epithelial-mesenchymal transition of cancer cells. Periostin also participates in the processes of angiogenesis and lymphangiogenesis, metastases of cancer cells, and remodeling of the extracellular matrix. Increased expression of periostin has been observed in various tumor types, including breast, NSCLC, colorectal, pancreatic, prostate, and ovarian cancers, as well as tumors of the head and neck, and glioblastomas. Many groups have recently reported on periostin’s key role in tumor progression, which suggests that periostin can be considered a potential therapeutic target

Expression of SATB1 protein in the ductal breast carcinoma tissue microarrays — preliminary study

Abstract: Special AT-rich sequence-binding protein 1 (SATB1) is a nuclear matrix protein which interacts with specific regions of DNA, ensuring its proper organization and function in the cell. The expression of SATB1 was primarily found in thymocytes, but its increased levels were observed in various types of cancers. However, the knowledge of the function and application possibilities of this protein is still limited. The aim of this study was to investigate the expression of SATB1 protein using immunohistochemistry and tissue microarray (TMA) technique and determine its possible relationship with the proliferative marker Ki-67, estrogen a (ER) and progesterone (PR) receptors as well as grade of histological malignancy (G). The study was performed on material of 48 archival invasive ductal breast cancers (IDC). The TMAs were prepared with the use of 0.6 mm diameter punches. Immunohistochemical reactions were carried out using antibodies against Ki-67, ER, PR and SATB1 proteins. The intensity of the nuclear reaction was evaluated using a light microscope and computer-assisted image analysis. Expression of Ki-67 and SATB1 protein was observed in 89.58% and 31.25% of cancer cases, respectively. 62.5% of tumors were classified as ER-positive, and 47.92% as PR-positive. Statistical analysis showed a moderate positive correlation between Ki-67 and SATB1 expression (r = 0.291, p = 0.045 independently on the receptor status, and r = 0.392, p = 0.032 in ER-negative tumors). The expression of the Ki-67 antigen increased with higher grade of histological malignancy (G). The results suggest that SATB1 protein may play an indirect role in the cell proliferation and should be evaluated in relation to the other markers. Further studies concerning determination of its role in cancer progression and metastasis, in terms of application as therapeutic target and prognostic marker, are recommended

Role of lymphangiogenesis in lung cancer.

Lung cancer represents one of the most frequent causes of death due to neoplastic disease in Poland and around the world. The high mortality which accompany neoplastic diseases used to be ascribed mainly to dissemination of cancerous cells. Studies on animal models suggest that tumour lymphangiogenesis represents the principal factor in the process of metastases formation. Lymphangiogenesis involves a process of formation of new lymphatic vessels from already existing lymphatic capillaries. Lymphangiogenesis is stimulated by vascular endothelial growth factors (VEGF) and other, recently reported factors, such as, e.g., cyclooxygenase 2, fibroblast growth factor 2, angiopoetin-1 and the insulin-resembling growth factor. In lymphangiogenesis a key role is played by neutropilin 2 or podoplanin and this promoted development of studies on lymphangiogenesis. Activation of VEGF-C/VEGF-D/VEGFR-3 axis increases motility and invasiveness of neoplastic cells, promotes development of metastases in several types of tumours such as, e.g., lung cancer, mammary carcinoma, cancers of the neck, prostate and large intestine. In recent years lymphangiogenesis provided topic of many studies. A positive correlation was detected between expressions of VEGF-C/D and VEGFR-3 in non-small cell lung cancer. In patients with lung cancer with high expression of VEGF-C a markedly abbreviated survival was noted. Positive correlation was detected between expression of VEGF-C and VEGF-D on one hand and expression of LYVE-1 on the other in sentinel lymph nodes with metastases of neoplastic cells in patients with non-small cell lung cancer. Also, high density of lymphatic vessels and high density of intraneoplastic microvessels proved to be independent poor prognostic indices in patients with non-small cell lung cancer. Extensive hope is linked to studies on inhibitors of lymphangiogenesis, which may improve results of treatment also in tumour patients

The morphological analysis of vasculature in thyroid tumours: immunoexpression of CD34 antigen.

Angiogenesis represents an important process manifested in tumour growth and in development of metastases. Using immunohistochemistry, the authors evaluated number of vessels in various nodular lesions of the thyroid (54 cases). Expression of CD34 antigen and microvessel density were evaluated in sections of archival paraffin blocks originating from the Department of Pathological Anatomy, University Medical School and the Lower Silesia Centre of Oncology in WrocĹaw, Poland. Microvessel density was assessed in ten different fields per section in "hot spots". Expression of CD34 was quantified using computerised image analysis and, then, mean micrvessel count (MVC) and microvessel area (MVA) were calculated. In thyroid tissue with benign lesions, the MVC (31.7) was higher than in neoplastic lesions (22.3), although no differences in MVA were observed. This observation points to differences in the size of newly formed vessels in individual nodular lesions of the thyroid

The usefulness of periostin determination in gynecology and obstetrics

Periostin (POSTN) is a multifunctional glycoprotein that belongs to the group of extracellular matrix (ECM) proteins. Dueto the molecular structure, cellular interactions, tissue locations as well functions of POSTN, we realize that its pivotalrole is organization and regulation of ECM microenvironment. In available databases there is a lack of data summarizingcurrent knowledge about POSTN expression in the field of gynecology and obstetrics. We conducted a search in PubMedof the National Library of Medicine and Google Scholar. Databases were extensively searched for all original and reviewarticles/book chapters published in English until December 2019 and related to periostin expression. All relevant articleswere reviewed and presented as appropriate.In the field of POSTN expression there is only one paper evaluating its involvement in cervical cancer cell metabolism andonly two studies analyzing its myometrial commitment: maintenance during pregnancy and induction of parturition inphysiology as well control of fibroids biology in pathology. Much more attention has been devoted to the expression ofdescribed protein in the endometriosis, and above all in ovarian cancer. Finally, a few studies carried out among pregnantwomen were presented.In this review study we presented current knowledge about periostin expression in the field of gynecology and obstetrics.Many achieved results are interesting and further studies are needed to verify some hypotheses. Structure, signalingpathways as well many functions of periostin are well-described. However, as it was clearly shown there is a lot of unknownissues which are waiting to be explored

Ceramide galactosyltransferase (UGT8) as a molecular marker of canine mammary tumor malignancy

 Thirty-two canine mammary tubulopapillary carcinomas and 14 simple adenomas were studied by immunohistochemistry for the expression of UDP-galactose:ceramide galactosyltransferase (UGT8). The majority of tissue specimens (57%) representing adenomas had no or weak reaction with anti-UGT8 antibodies (0-2 pts according to IRS scale) in comparison to the majority of carcinomas (90%) which stained with high intensities (3-9 pts according to IRS scale). When the average values of the reaction intensities (IRS) for malignant and benign tumors were compared, using the Mann-Whitney U-test, significant differences in UGT8 expression between them were found (P < 0.001). Mammary tubulopapillary carcinomas were further analyzed by IHC and the same rabbit polyclonal antibody directed against UGT8 according to their malignancy grade. It was found that the level of UGT8 increased in tumor specimens together with their grading. A comparison of the average values of the reaction intensity (IRS scale) revealed a significant difference (Mann-Whitney U-test, P < 0.05) in UGT8 expression between tumors representing malignancy grades G3 and G1. Based on the obtained results, it is proposed that UGT8 is associated with malignancy of canine mammary gland cells and may have a potential value as a diagnostic marker.

Metallothioneins in the lung cancer

Metallothioneins (MTs) are low weight proteins involved in several key cellular processes such as metal ions homeostasis, detoxification and scavenging of free radicals. Four groups of MTs are distinguished: MT-1, MT-2, MT-3 and MT-4. Regardless of the type, MTs are characterized by high content of cysteine, responsible for their biological properties such as binding of relevant zinc and copper ions, as well as toxic ions such as lead and cadmium. MTs were additionally shown to protect cells against oxidative stress damage and participate in differentiation, proliferation and/or apoptosis of normal and cancer cells. Many studies of different neoplasms showed association of elevated MTs levels with occurrence of chemo- and radiotherapy resistance and poor patients’ outcome. In this review, we summarize and discuss the potential mechanism of action of metallotioneins in lung physiology and pathology

LAM cells biology and lymphangioleiomyomatosis

Progressive lung tissue destruction in lymphangioleiomyomatosis (LAM) occurs as a result of excessive proliferation of LAM cells caused by a mutation in one of the tuberous sclerosis complex suppressor genes, TSC1 or TSC2. These cells show constitutive activation of the mammalian target of rapamycin (mTOR) pathway and many of the mTOR-related kinases such as Akt, Erk, S6K1 and S6. Phenotype of LAM cells differs considerably depending on their microenvironment. LAM cells show differences in morphology, size and expression of various factors depending on their location in the tumor or body fluids. The presence of LAM cells in blood, urine, bronchoalveolar lavage fluid (BALF), and chyle proves their ability to metastasis. Antigens of smooth muscle cells are expressed in most LAM cells. Some of these cells are immunoreactive with HMB-45 antibody, which is used for the immunohistochemical diagnosis of LAM. Receptors for estrogen and progesterone may also be expressed in these cells, which probably is associated with the fact that LAM occurs almost exclusively in women of childbearing age. LAM cells via increased production of metalloproteinases are involved in the destruction of the extracellular matrix, as well as the remodeling and damage of lung tissue. Sporadic LAM occurs extremely rarely. Therefore a good experimental model of this disease is necessary. To date, several animal and human cell lines, which both genetically and phenotypically resemble LAM cells, have been obtained. These cell lines, derived from LAM nodule or an angiomyolipoma, are usually characterized by a mutation of the TSC2 gene, expression of smooth muscle cell antigens such as a-smooth muscle actin (aSMA) or S6K1 and S6 protein hyperphosphorylation. Presently, there is no commercially available cell line representing a good model of LAM. A better understanding of LAM cell biology is necessary for creating a useful model in vitro for further exploration of both LAM pathomechanisms and more general mechanisms of carcinogenesis. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 1–10

Adventitial lymphatics of internal carotid artery in healthy and atherosclerotic vessels.

OBJECTIVESPresence of lymphatics in adventitia of major arteries remains controversial. Presence of lymphatics in adventitia of internal carotid artery was not documented and its relation to atherosclerosis was not studied. The aim of our study was to evaluate presence of lymphatic vessels in adventitia of internal carotid artery in healthy and atherosclerotic arteries.METHODSFragments of arterial wall of internal carotid artery were obtained during the surgical eversion endarterectomy in 15 patients with internal carotid artery stenosis and 2 healthy organ donors. 21 arteries were studied. Patients age ranged from 56 to 77 years. Fragments of arterial wall were embeded in paraffin. Lymphatics of arterial adventitia were visualized with immunohistochemistry using LYVE-1 and anty-podoplanin antibodies.RESULTSThe lymphatic vessels were visualized in adventitia of 20 carotid arteries. The serial sections have revealed that both LYVE-1 and podoplanin have identical specificity for lymphatic endothelium Number of lymphatics in adventitia significantly correlated with thickness of intima (