Pancreatic cancer cells express CD44 variant 9 and multidrug resistance protein 1 during mitosis

Kiuchi, Shizuka; Ikeshita, Shunji; Miyatake, Yukiko; Kasahara, Masanori

doi:10.1016/j.yexmp.2014.12.001

Cited by 22 publications

(17 citation statements)

References 32 publications

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“…Upregulation of CD44 is correlated with tumor progression and the metastatic phenotype in many cancers, including pancreatic cancer [52]. All six PCC cultures demonstrated a strong expression of pan-CD44, consistent with previously reported data in human PDAC-derived carcinoma cells [53].…”

Section: Discussionsupporting

confidence: 89%

Establishment and Characterization of Paired Primary Cultures of Human Pancreatic Cancer Cells and Stellate Cells Derived from the Same Tumor

Amrutkar

Larsen

Aasrum

et al. 2020

Cells

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis, and its treatment remains a challenge. As the existing in vitro experimental models offer only a limited resemblance to human PDAC, there is a strong need for additional research tools to better understand PDAC tumor biology, particularly the impact of the tumor stroma. Here, we report for the first time the establishment and characterization of human PDAC-derived paired primary monolayer cultures of (epithelial) cancer cells (PCCs) and mesenchymal stellate cells (PSCs) derived from the same tumor by the outgrowth method. Characterization of cell morphology, cytostructural, and functional profiles and proteomics-based secretome analysis were performed. All PCCs harbored KRAS and TP53 mutations, and expressed cytokeratin 19, ki-67, and p53, while the expression of EpCAM and vimentin was variable. All PSCs expressed α-smooth muscle actin (α-SMA) and vimentin. PCCs showed a significantly higher growth rate and proliferation than PSCs. Secretome analysis confirmed the distinct nature of PCCs as compared to PSCs and allowed identification of potential molecular regulators of PSC-conditioned medium (PSC-CM)-induced migration of PCCs. Paired primary cultures of PCCs and PSCs derived from the same tumor specimen represent a novel experimental model for basic research in PDAC tumor biology.

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Section: Discussionsupporting

confidence: 89%

Establishment and Characterization of Paired Primary Cultures of Human Pancreatic Cancer Cells and Stellate Cells Derived from the Same Tumor

Amrutkar

Larsen

Aasrum

et al. 2020

Cells

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“…In this study, we used serum-containing medium because PANC-1 cells most rapidly form large spheres under these conditions. The spheres generated from these cells expressed high mRNA levels of CSC markers, suggesting that they contain CSCs (7,13,(17)(18)(19). A previous study showed that PANC-1 cells grown in a serum-containing medium formed clusters that were heterogeneous for dye efflux, while cells grown in the serum-free medium with supplements commonly used to culture stem cells gave rise to colonies that varied in their ability to efflux dye and respond to verapamil (27).…”

Section: Discussionmentioning

confidence: 98%

“…To confirm the stemness of the PANC-1 spheres, we screened the spheres for expression of CSC markers, including Oct4, sex determining region Y-box 2 (Sox2), nestin, CD24, and CD44v9 (7,(17)(18)(19). Notably, the mRNA expression level of each of these markers was higher in PANC-1 spheres than in adherent cells ( Fig.…”

Section: Rt-qpcrmentioning

confidence: 98%

Electron microscopic analysis of different cell types in human pancreatic cancer spheres

et al. 2017

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Abstract. Cancer stem cells (CSCs), which are pluripotent and self-renewable, contribute to the initiation and metastasis of cancer, and are responsible for resistance to chemotherapy and radiation. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer that is associated with a high incidence of distant metastasis and recurrence. Sphere formation reveals cell proliferation under nonadherent conditions and is commonly used to identify CSCs; measurements of the number, area and volume of the spheres are used to estimate stemness of PDAC cells. However, detailed morphological analysis of such spheres has not been performed. The aim of the present study was to examine the morphology of spheres isolated from PANC-1 human pancreatic cancer cells via scanning electron microscopy (SEM) and transmission electron microscopy (TEM). PANC-1 cells formed round to irregular oblong spheres within 1 week following seeding in ultra-low-attachment plates. These spheres exhibited higher levels of expression of CSC markers, including nestin, sex determining region Y-box 2, and CD44 containing variant exon 9, compared with adherent cells. SEM analysis revealed that the spheres exhibited a grape-like appearance, harboring cancer cells with smooth or rough surfaces. Similarly, TEM analysis detected cancer cells with varying surface types within the spheres: Those with smooth surfaces, irregular large protrusions, protrusions and a small number of microvilli, and those with many microvilli throughout the entire cell surface. These morphological differences among cancer cells may be indicative of different stages in the differentiation process, from CSCs to non-CSCs, within the spheres.

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“…For example, a 2014 study of CD44 isoforms in metastatic melanoma cells demonstrated that expression of a CD44 variant (variable exons 8-10) resulted in loss of endothelial junctions and higher invasive potential compared to melanoma cells expressing standard CD44s [39]. A similar study in 2014 demonstrated that expression of a CD44v9 (variable exon 9) isoform was associated with a high expression of multi-drug resistance protein 1 (MDR1; P-glycoprotein) in pancreatic cancer cells [40]. P-glycoprotein is the primary ABC-transporter in multi-drug resistant cells that functions as a drug efflux pump.…”

Section: Expression Profile Of Cd44 In Different Cellsmentioning

confidence: 99%

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

Mattheolabakis

Milane

Singh

et al. 2015

Journal of Drug Targeting

472

310

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Cluster of differentiation-44 (CD44) is a ubiquitously present glycoprotein on the surface of mammalian cells that plays a significant role in a number of biological functions. Since the discovery that the receptor is over-expressed in a variety of solid tumors, such as pancreatic, breast and lung cancer, many studies have focused on methods for targeting CD44 in an attempt to improve drug delivery and discrimination between healthy and malignant tissue, while reducing residual toxicity and off-target accumulation. In this review, we describe CD44 receptor biology and its involvement in the different stages of tumor growth and metastasis, as well as methods currently used for targeting the receptor. Hyaluronic acid, the primary CD44 binding molecule, has proved a significant ally in developing nanocarriers that demonstrate preferential tumor accumulation and increased cell uptake. We outline a number of research approaches from the current literature that take advantage of hyaluronic acid's targeting ability and describe the possible advantages for each approach. The value of CD44 targeting can be easily appreciated from the number of different approaches that have reached clinical trials.

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Pancreatic cancer cells express CD44 variant 9 and multidrug resistance protein 1 during mitosis

Cited by 22 publications

References 32 publications

Establishment and Characterization of Paired Primary Cultures of Human Pancreatic Cancer Cells and Stellate Cells Derived from the Same Tumor

Establishment and Characterization of Paired Primary Cultures of Human Pancreatic Cancer Cells and Stellate Cells Derived from the Same Tumor

Electron microscopic analysis of different cell types in human pancreatic cancer spheres

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

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