Hyaluronic acid (HA) is conjugated as targeting moiety for CD-44 (cancer stem cell marker) to fabricate a complete targeted drug delivery vehicle specific for pancreatic cancer.
The aims of this study were 1) to investigate the mRNA pattern of CD44 variants in three primary (MIA PaCa 2, PANC-1, PSN-1) and two metastatic (CAPAN-1, SUIT-2) pancreatic cancer (PC) cell lines; 2) to ascertain whether the genetic transfer of CD44s and CD44v10 modifies the adhesion of PC cells to the extracellular matrix (ECM) in vitro and their metastatic behavior in vivo.
In the present study, we found that isolated triple-marker-positive (CD44(+)/CD133(+)/EpCAM(+)) cells of human PC MiaPaCa-2 and L3.6pl cells behave as CSLCs.
We identified HAb18G/CD147 as a novel upstream activator of STAT3, which interacts with CD44s and plays a critical role in the development of pancreatic cancer.
Considering the overexpression of mRNA, it was tentatively suggested that LY6E, TACSTD1, and CD44 proteins may act as surface markers for sorting pancreatic cancer stem cells with fluorescence-activated cell sorter/magnetic-activated cell sorter.
Based on our data, β-catenin may be involved in cancer invasion in pancreatic cancer, and it is not associated with CD44, the invasion related protein.
This study has used the following in vitro and in vivo techniques for the investigation of exceptional anticancer drug FL118's efficacy in treatment of resistant pancreatic cancer: cell culture; immunoblotting analysis to test protein expression; DNA sub-G1 flow cytometry analyses to test cell death; MTT assay to test cell viability; pancreatic cancer stem cell assays (fluorescence microscopy tracing; matrigel assay; CD44-positive cell colony formation assay); human luciferase-labeled pancreatic tumor orthotopic animal model in vivo imaging; pancreatic cancer patient-derived xenograft (PDX) animal models; and toxicology studies with immune-competent BALB/cj mice and beagle dogs.
This strategy is unclear for treatment of pancreatic cancer, and little is known about how anti-CD44s affect pancreatic cancer initiation or recurrence after radiotherapy.
In conclusion, CD44(+) /CD24(+) /EpCAM(+) expression overlapped with poorly differentiated cells and possessed high proliferative potential in clinical pancreatic cancer.
These data indicate that cancer stem-like cells were expanded during the acquisition of gemcitabine resistance and in therapeutic application, targeted therapy against the CD44 or ABC transporter inhibitors could be applied to overcome drug resistance in the treatment of pancreatic cancer.
Here we show that isolated CD44(+)/CD133(+)/EpCAM(+) cells (triple-marker-positive cells) from human PC cell lines, MiaPaCa-2 and L3.6pl cells, display aggressive characteristics, such as increased cell growth, clonogenicity, cell migration, and self-renewal capacity, which is consistent with overexpression of CSLC signatures/markers.
This study sets the stage for CD44 and MT1-MMP as therapeutic targets in pancreatic cancer, for which small molecule or biologic inhibitors are available.
Considering the overexpression of mRNA, it was tentatively suggested that LY6E, TACSTD1, and CD44 proteins may act as surface markers for sorting pancreatic cancer stem cells with fluorescence-activated cell sorter/magnetic-activated cell sorter.
Although most of the pancreatic cancer cell lines express a complex but identical pattern of variant CD44 gene transcripts, only one higher molecular weight CD44 isoform can be detected in a subset of pancreatic cancer cell lines in Western blot analysis.
We analyzed whether CD44 and ZEB1 regulate each other and show that ZEB1 controls CD44s splicing by repression of ESRP1 in breast and pancreatic cancer.
The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity.
CD133(+)/CD44(+)/Oct4(+)/Nestin(+) stem-like cells isolated from Panc-1 cell line may contribute to multi-resistance and metastasis of pancreatic cancer.
Exon specific analysis revealed an altered splice pattern of CD44, similar to that in pancreatic cancer, in 12.5% of the chronic pancreatitis specimens.