Novel CD44v6 isoform overexpressed in metastases of pancreatic adenocarcinoma

Rall, Christopher; Rustgi, Anil K.

doi:10.1016/0016-5085(95)24199-x

Cited by 45 publications

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“…Aside from the possible biological consequence of CD44 variant expression the complex patterns obtained may prove to be of diagnostic, prognostic or even therapeutic value. 43 Expression of variants containing exon v6 have been related to increased metastatic potential in breast and pancreatic cancers and non-Hodgkin's lymphoma, [44][45][46] a poor prognosis in acute myeloid leukemia 24 and decreased aggressiveness in ovarian and oral cancers. 47,48 In non-Hodgkin's lymphoma, the inclusion of additional variant exons with exon v6 reversed the effect seen with exon v6 alone.…”

Section: Discussionmentioning

confidence: 99%

Expression of CD44 variant exons in acute myeloid leukemia is more common and more complex than that observed in normal blood, bone marrow or CD34+ cells

2000

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Section: Discussionmentioning

confidence: 99%

Expression of CD44 variant exons in acute myeloid leukemia is more common and more complex than that observed in normal blood, bone marrow or CD34+ cells

2000

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“…Recent clinicopathological studies have revealed that the expression of individual variant exons is associated with poorer prognosis in several malignancies; for example, that of exon 14 (v9) is increased in gastric adenocarcinoma, 21) that of exon 11 (v6) in colon, breast, 22,23) and pancreas 24,25) cancers, and that of exon 7 (v2) in breast 5 To whom correspondence should be addressed.…”

Section: )mentioning

confidence: 99%

“…Moreover, in a recent study, 20) direct comparison of Southern blots with western blots from matched tumor cell line extracts indicated that most of the diverse mRNA isoforms are not detectably translated into proteins. These findings, together with data from reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis, show that the overexpression at the protein level involves only a minority of aberrant RNA transcripts.Recent clinicopathological studies have revealed that the expression of individual variant exons is associated with poorer prognosis in several malignancies; for example, that of exon 14 (v9) is increased in gastric adenocarcinoma, 21) that of exon 11 (v6) in colon, breast, 22,23) and pancreas 24,25) cancers, and that of exon 7 (v2) in breast 5 To whom correspondence should be addressed. …”

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Expression of CD44 Variants and Its Association with Survival in Pancreatic Cancer

Gotoda

Matsumura

Kondo

et al. 1998

Japanese Journal of Cancer Research

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Since the CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, we examined whether or not v6 is a useful marker for evaluating the prognosis of pancreatic cancer patients. In addition, we attempted to assess the clinicopathological implications for pancreatic cancer of the variant 2 (v2) isoform using a recently developed monoclonal antibody against a v2 epitope. The expression of CD44 variants was evaluated immunohistochemically in paraffin-embedded pancreatic cancer tissues from 42 patients who were confirmed surgically and histologically to have received curative resection. An indirect immunoperoxidase method was used with monoclonal antibodies against epitopes of the standard (CD44s) Key words: CD44 variants -Pancreatic cancer -Metastasis -Prognosis -Immunohistochemistry CD44 is a heavily glycosylated cell surface molecule which is involved in cell-cell and cell-matrix interactions 1, 2) and mediates several functions, such as extracellular matrix cell adhesion, 3, 4) lymphocyte homing, 5,6) T cell activation 7) and tumor metastasis. 7,8) The CD44 family of polymorphic transmembrane glycoproteins is encoded by a complex gene 7,[9][10][11][12] that occupies a stretch of 60-80 kD assigned to the human chromosomal locus 11p13. Its human form is composed of at least 21 exons, 10 of which are constitutively expressed on almost all cell types to produce a heavily glycosylated 85-90 kD isoform known as standard form CD44s (Fig. 1). The remaining exons can be alternatively spliced in various combinations, and their products are incorporated into the polypeptide backbone encoded by the standard form exons. This results in a large array of protein isoforms (CD44v) which are differentially expressed in various tissues and at various stages in development. 13)Recently, it was demonstrated that the expression of one variant isoform of CD44 distinguished metastatic from non-metastatic pancreatic carcinoma cell lines in the rat.8) Evidence that CD44v itself has a role in metastasis came from the demonstration that transfection with cDNA encoding this isoform converted non-metastatic carcinoma rat cells into metastatic cells. 8) Although the functions of CD44v isoforms in humans remain unclear, it is thought that CD44v isoforms play an important role in the growth and metastasis of several kinds of tumors. [14][15][16][17][18] It has been demonstrated that the disturbed activity of the CD44 gene in malignant tumors results in the accumulation of immature mRNA transcripts containing introns 10,19) from the CD44 gene. Moreover, in a recent study, 20) direct comparison of Southern blots with western blots from matched tumor cell line extracts indicated that most of the diverse mRNA isoforms are not detectably translated into proteins. These findings, together with data from reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis, show that the overexpression at the protein level involves only a minority of aberrant RNA transcripts.Recent clinic...

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“…Both prostate and bladder tumors lose protein antigen expression of CD44s 11,12 and CD44v6 11,13 as the grade of the tumor increases, whereas amplification in CD44v6 is noted with metastatic phenotype of pancreatic cancer 14 and increasing grade of breast cancer. 15,16 Inclusion of single or contiguous variant exons has been described by RT-PCR and sequencing in many benign and cancer tissues.…”

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“…15,16 Inclusion of single or contiguous variant exons has been described by RT-PCR and sequencing in many benign and cancer tissues. 5,6,[14][15][16][17][18][19][20][21][22][23] We, 11 and subsequently others, 12,13 showed that PC loses immunohistochemical expression of CD44s and some CD44v isoforms. CD44v6 was absent by Figure 1 Splice variant CD44 exons are situated in the extracellular domain.…”

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confidence: 99%

Prostate cancer invasion is influenced more by expression of a CD44 isoform including variant 9 than by Muc18

Omara-Opyene

Qiu

Shah

et al. 2004

Laboratory Investigation

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The standard form of cell adhesion glycoprotein CD44 is a metastasis suppressor in prostate cancer. However, we previously showed by RT-PCR and Western blotting that cancer overexpresses unique CD44 variant v7-v10 isoforms. Muc18 is another cell adhesion marker reportedly overexpressed by prostate cancer. Matched frozen section-confirmed tumor and benign tissues were harvested from 10 prostatectomy specimens and tumor was microdissected from two lymph node metastases. Tissues were homogenized for RNA preparations, and RT-PCR was performed for the CD44v7-v10 sequence. In cultured prostate cancer cells, we caused RNA interference against CD44v9 and/or Muc18. We used PC3M cells and a derivative cell line called G s a, that constitutively expresses this G-protein and is more invasive. Lipofection was performed for a green fluorescent protein plasmid and for two 22-mer DNA fragments, cloned into a plasmid expression vector to generate hairpin, interfering dsRNA. Assays for invasion into Matrigel, a basement membrane matrix, were performed in 4-5 experiments. RT-PCR demonstrated expression of a 608 bp band representing CD44v7-v10 or a 638 bp band of Prostate cancer remains a public health problem of enormous magnitude; it is the second most common cause of cancer fatality among North American men and the most common in Great Britain. Only a minority of all cases invade locally and metastasize, thus requiring altered expression of cell adhesion molecules to allow tumor cell detachment, migration through a stromal matrix, and lymphovascular invasion.CD44, a family of transmembrane glycoproteins involved in homotypic cell, cell-matrix, and cellcytoskeletal interaction, holds promise as a prostate tumor marker. The extracellular domain of CD44 binds numerous matrix substituents: hyaluronic acid, heparin-affinity growth factors, vascular endothelial growth factor, p185 HER2 , epidermal growth factor, and hepatocyte growth factor. Its intracellular domain binds to ezrin, radixin, moesin and merlin, which interact with the cytoskeleton; notably, neutral endopeptidase 24.11 competes with CD44 for this interaction. 1 CD44 also binds directly to the cytoskeletal substituent ankyrin, thus determining cell and tissue architectural form. 2 CD44 is an oncodevelopmental protein, with roles in

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Novel CD44v6 isoform overexpressed in metastases of pancreatic adenocarcinoma

Cited by 45 publications

References 0 publications

Expression of CD44 variant exons in acute myeloid leukemia is more common and more complex than that observed in normal blood, bone marrow or CD34+ cells

Expression of CD44 variant exons in acute myeloid leukemia is more common and more complex than that observed in normal blood, bone marrow or CD34+ cells

Expression of CD44 Variants and Its Association with Survival in Pancreatic Cancer

Prostate cancer invasion is influenced more by expression of a CD44 isoform including variant 9 than by Muc18

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