Matrigel‐induced acinar differentiation is followed by apoptosis in HSG cells

Szlávik, Vanda; Vág, János; Markó, Károly; Demeter, Kornél; Madarász, Emı́lia; Oláh, Imré; Zelles, T; O’Connell, Brian; Varga, Gábor

doi:10.1002/jcb.21404

Cited by 21 publications

(24 citation statements)

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“…Although survivin has been detected during embryonic submandibular salivary gland development, presumably mediating epithelial cell survival,37 and may participate in matrigel-induced acinar differentiation of salivary gland cells,38 the presence of survivin in the tumor cells of SGTs had not been previously studied. In the present study, all benign and malignant SGTs expressed survivin, suggesting that aberrations in survivin expression participate in the neoplastic transformation of salivary gland cells.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of the oncogenic molecules active Stat3 and survivin in benign and malignant salivary gland tumors

Nikitakis

Scheper

Papanikolaou

et al. 2009

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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Objective Signal transducer and activator of transcription 3 (Stat3) and survivin have been shown to exert oncogenic effects in various human neoplasms. The purpose of this study was to evaluate the expression of the tyrosine phosphorylated (active) Stat3 and survivin in various benign and malignant salivary gland tumors (SGTs). Study design Eighty-six SGTs (65 malignant and 21 benign tumors of various histopathologic subtypes) were immunohistochemically stained with anti-survivin or anti-phosphorylated tyrosine-705 (p-tyr) Stat3 antibodies. Immunohistochemical reactivity was graded in a semi-quantitative manner; a combined score of immunohistochemical positivity (0–6) was calculated for each tumor by adding the individual scores for percentage of tumor cells (0–3) and intensity of staining (0–3). Results Survivin was immunohistochemically detected in all studied benign and malignant SGTs; p-tyr Stat3 was also detected in the majority (91%) of SGTs. The average combined scores for survivin and p-tyr Stat3 immunohistochemical expression in the studied malignant SGTs was 4.40 and 3.35, respectively; the corresponding combined scores for survivin and p-tyr Stat3 in the studied benign SGTs were 4.37 and 3.22, respectively. No statistically significant differences (p>0.05) in p-tyr Stat3 or survivin expression were detected between the benign and malignant groups, or among the various examined histopathological subtypes of SGTs. In contrast, normal salivary gland elements in the vicinity of the studied tumors revealed only weak and focal survivin or p-tyr Stat3 immunoreactivity, mainly localized to ductal and mucous cells. Conclusions Our data indicate an almost universal expression of activated Stat3 and survivin in benign and malignant SGTs. Considering the well-established proliferative and anti-apoptotic properties of these molecules and their functional interrelationship, selective targeting techniques against Stat3 and/or survivin may represent promising therapeutic strategies against neoplasms of salivary gland origin.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of the oncogenic molecules active Stat3 and survivin in benign and malignant salivary gland tumors

Nikitakis

Scheper

Papanikolaou

et al. 2009

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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“…Although the acini morphologies are found in several other epithelia in 3D systems [Pollack et al, 1998;Debnath et al, 2002;Szlavik et al, 2008] and some rodent hepatocytes [Bissell et al, 1987;Dunn et al, 1991;Haouzi et al, 2005], it seldom happens in human hepacotyes. It has been reported that a series of adjacent small lumens are formed in primary rat hepatocytes in 3D culture [Bissell et al, 1987;Dunn et al, 1991;Abu-Absi et al, 2002], and relative large lumens with small ones are also detected in the immortal murine mhAT3F hepatocytes [Haouzi et al, 2005].…”

Section: Discussionmentioning

confidence: 96%

“…It occurs in the lumen of 3D cultures of salivary gland [Szlavik et al, 2008], kidney [Pollack et al, 1998], and mammary epithelium [Debnath et al, 2002;Hebner et al, 2008], which is believed to reflect the physiological death during development in these organs. In our study, apoptosis clearly contributes to the lumen formation in QSG-7701 spheroids.…”

Section: Discussionmentioning

confidence: 99%

“…organization [Haouzi et al, 2005;Joraku et al, 2007;Szlavik et al, 2008;Xu et al, 2009]. The subendothelial space of hepatocytes in liver contains constituent proteins of a basal lamina, which affects hepatocelluar morphology and function [Bissell et al, 1987;Bissell and Choun, 1988].To better control the differentiation and cellular architecture of hepatocytes in vitro, the use of various components of the ECM has been explored in rodent hepatocyte culture [Moghe et al, 1996;Haouzi et al, 2005], and human primary cell culture [Kono et al, 1995].…”

Section: Discussionmentioning

confidence: 99%

“…Unlike 2D cultures, the 3D culture provides a unique opportunity to model the architecture of epithelium in vitro. Mammary epithelial cells in 3D culture form growth-arrested polarized acini with a hollow lumen [Debnath et al, 2002], human salivary gland cells are capable of morphogenesis and differentiation to cysts in 3D culture [Joraku et al, 2007;Szlavik et al, 2008], thyroid cells organize into follicles [Toda and Sugihara, 1990;Yap et al, 1994], and Madin-Darby Canine Kidney (MDCK) cells form cysts and tubules [Pollack et al, 1998;Lin et al, 1999] in 3D cultures. Apoptosis has been shown to be critical for creating luminal space during acinar morphogenesis in MCF-10A mammary gland [Debnath et al, 2002] and HSG salivary gland 3D cultures [Szlavik et al, 2008].…”

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QSG‐7701 human hepatocytes form polarized acini in three‐dimensional culture

Zhang

Zhao

2010

J of Cellular Biochemistry

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Hepatocytes are polarized and fulfill a variety of liver-specific functions in vivo; but the polarized tissue structure and many of these functions are lost when the cells are cultured on plastic. To recapitulate the polarized structure and tissue-specific function of liver cells in culture, we established a three-dimensional (3D) culture assay with the human hepatocyte line QSG-7701. In 3D Matrigel culture, QSG-7701 cells formed polarized spheroids with a center lumen, which is reminiscent of bile canaliculi in the liver. Immunofluoresence analysis showed that F-actin bundles and radixin were mainly located at the apical membrane and that alpha6 and beta1 integrins were localized basally in 3D culture. Lumen formation was associated with the selective apoptosis of centrally located cells and was accompanied by proliferative suppression during acinar development. Compared to QSG-7701 cells in 2D or agarose gel cultures, the cells in 3D Matrigel culture maintained a given direction of biliary excretion and acquired higher levels of cytochrome P450 and albumin expression. Our study shows that the immortal human hepatocytes, QSG-7701, in 3D Matrigel culture reacquire cardinal features of glandular epithelium in vivo, providing an ex vivo model to study liver-specific function and tumorigenesis.

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Encapsulation of Primary Salivary Gland Acinar Cell Clusters and Intercalated Ducts (AIDUCs) within Matrix Metalloproteinase (MMP)‐Degradable Hydrogels to Maintain Tissue Structure and Function

Song

Sharipol

Uchida

et al. 2022

Adv Healthcare Materials

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Progress in the development of salivary gland regenerative strategies is limited by poor maintenance of the secretory function of salivary gland cells (SGCs) in vitro. To reduce the precipitous loss of secretory function, a modified approach to isolate intact acinar cell clusters and intercalated ducts (AIDUCs), rather than commonly used single cell suspension, is investigated. This isolation approach yields AIDUCs that maintain many of the cell-cell and cell-matrix interactions of intact glands. Encapsulation of AIDUCs in matrix metalloproteinase (MMP)-degradable PEG hydrogels promotes self-assembly into salivary gland mimetics (SGm) with acinar-like structure. Expression of Mist1, a transcription factor associated with secretory function, is detectable throughout the in vitro culture period up to 14 days. Immunohistochemistry also confirms expression of acinar cell markers (NKCC1, PIP and AQP5), duct cell markers (K7 and K5), and myoepithelial cell markers (SMA). Robust carbachol and ATP-stimulated calcium flux is observed within the SGm for up to 14 days after encapsulation, indicating that secretory function is maintained. Though some acinar-to-ductal metaplasia is observed within SGm, it is reduced compared to previous reports. In conclusion, cell-cell interactions maintained within AIDUCs together with the hydrogel microenvironment may be a promising platform for salivary gland regenerative strategies.

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Matrigel‐induced acinar differentiation is followed by apoptosis in HSG cells

Cited by 21 publications

References 56 publications

Immunohistochemical expression of the oncogenic molecules active Stat3 and survivin in benign and malignant salivary gland tumors

Immunohistochemical expression of the oncogenic molecules active Stat3 and survivin in benign and malignant salivary gland tumors

QSG‐7701 human hepatocytes form polarized acini in three‐dimensional culture

Encapsulation of Primary Salivary Gland Acinar Cell Clusters and Intercalated Ducts (AIDUCs) within Matrix Metalloproteinase (MMP)‐Degradable Hydrogels to Maintain Tissue Structure and Function

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