RHAMM expression and isoform balance predict aggressive disease and poor survival in multiple myeloma

Maxwell, Christopher A.; Rasmussen, Erik; Zhan, Fenghuang; Keats, Jonathan J.; Adamia, Sophia; Strachan, Erin; Crainie, Mary; Walker, Ronald C.; Belch, Andrew R.; Pilarski, Linda M.; Barlogie, Bart; Shaughnessy, John D.; Reiman, Tony

doi:10.1182/blood-2003-11-4079

Cited by 96 publications

(86 citation statements)

References 32 publications

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“…Recent studies indicate that CD44 is functionally important in leukemia stem cells (Jin et al, 2006;Krause et al, 2006) and other studies point to a possible role for another hyaluronan-binding protein, Rhamm, in myeloma progenitors (Crainie et al, 1999;Maxwell et al, 2004). Hyaluronan appears to have a role in normal stem cell behavior (Avigdor et al, 2004;Matrosova et al, 2004;Nilsson et al, 2003;Pilarski et al, 1999) and hyaluronan synthases are altered in myeloma progenitors (Adamia et al, 2005;Calabro et al, 2002).…”

Section: Regulation Of Cancer Stem Cell Properties By Hyaluronan and mentioning

confidence: 99%

Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance

Toole

Slomiany

2008

Drug Resistance Updates

161

146

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Hyaluronan is not only an important structural component of extracellular matrices but also interacts with cells during dynamic cell processes such as occur in cancer. Consequently, interactions of hyaluronan with tumor cells play important cooperative roles in various aspects of malignancy. Hyaluronan binds to several cell surface receptors, including CD44, thus leading to co-regulation of signaling pathways that are important in regulation of multidrug resistance to anticancer drugs, in particular anti-apoptotic pathways induced by activation of receptor tyrosine kinases. Emmprin, a cell surface glycoprotein of the Ig superfamily, stimulates hyaluronan production and downstream signaling consequences. Emmprin and CD44 also interact with various multidrug transporters of the ABC family and monocarboxylate transporters associated with resistance to cancer therapies. Moreover, hyaluronan-CD44 interactions are critical to these properties in the highly malignant, chemotherapy-resistant cancer stem-like cells. Perturbations of the hyaluronan-CD44 interaction at the plasma membrane by various antagonists result in attenuation of receptor tyrosine kinase and transporter activities and inhibition of tumor progression in vivo. These antagonists, especially small hyaluronan oligomers, may be useful in therapeutic strategies aimed at preventing tumor refractoriness or recurrence due to drug-resistant sub-populations within malignant cancers.

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Section: Regulation Of Cancer Stem Cell Properties By Hyaluronan and mentioning

confidence: 99%

Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance

Toole

Slomiany

2008

Drug Resistance Updates

161

146

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“…As the isoform balance of some aberrantly spliced genes in cancer cells was reported to be a prognostic marker (18,19), we first determined rab15 isoform balance measured by the rab15 cn / rab15…”

Section: Differential Expression Of Rab15mentioning

confidence: 99%

“…In the case of hyaluronan synthase 1 (HAs1) and receptor for hyaluronan-mediated motility (rHAMM), their aberrant splicing are associated with multiple myeloma, and their isoform balance is shown to be a prognostic marker (18,19). Although an increasing number of cancer-associated alternative splicing events are identified, alternative splicing of rab proteins remains to be characterized in neuroblastoma (20,21).…”

Section: Introductionmentioning

confidence: 99%

“…An increasing number of genes including HAs1 and rHAMM are shown to predict clinical outcome depending on the differential expression of alternatively spliced isoforms in cancer patients (18)(19)(20)(21). Although alternative splicing events of rab proteins remain to be characterized in neuroblastoma, rab6A and rab28 are reported to contain alternatively spliced isoforms.…”

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confidence: 99%

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Rab15 expression correlates with retinoic acid-induced differentiation of neuroblastoma cells

Nishimura

Pham²,

Hartomo³

et al. 2011

Oncol Rep

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Abstract. neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of pediatric cancer deaths. Although retinoic acid (rA) is currently used to treat high-risk neuroblastoma patients in the clinic, rA-responsiveness is variable and unpredictable. since no alterations in the rA-signaling pathway have been found in neuroblastoma cells, molecules correlated with rA-induced differentiation will provide predictive markers of rA-responsiveness for clinical use. the rab family of small G proteins are key regulators of membrane traffic and play a critical role in cell differentiation and cancer progression. Although an increasing number of cancer-associated alternative splicing events have been identified, alternative splicing of rab proteins remains to be characterized in neuroblastoma. In the present study, we focused on rab15 that was originally identified as a brain-specific Rab protein and regulates the endocytic recycling pathway. We identified alternatively spliced rab15 isoforms designated as rab15 cn and rab15An in neuroblastoma cells. rab15 cn was composed of 7 exons encoding 212 amino acids and showed brain-specific expression. Alternative splicing of exon 4 generated rab15An that was predicted to encode 208 amino acids and was predominantly expressed in testis. rA induced neuronal differentiation of neuroblastoma BE(2)-C cells and specifically up-regulated rab15 cn expression. reciprocally, rA-induced differentiation was observed in rab15 cn -expressing Be(2)-c cells in preference to rab15An -expressing Be(2)-c cells. Furthermore, rab15 cn expression was also specifically up-regulated during rA-induced differentiation of newly established neuroblastoma cells from high-risk patients. these results suggest that rab15 expression correlates with rA-induced differentiation of neuroblastoma cells.

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“…Loss of Ephrin B2 receptor (EphB2) and the metastasis suppressor Raf-1 kinase inhibitor protein (RKIP) have been linked with poor outcome (Jubb et al, 2005;Al-Mulla et al, 2006), whereas expression of Ki67 and p53 have led to conflicting reports (Kyzer and Gordon, 1997;Munro et al, 2005). The receptor for hyaluronic acid-mediated motility (RHAMM) mediates both Ras and TGF-b signalling pathways and is associated with poor prognosis in a variety of tumour entities (Wang et al, 1998;Maxwell et al, 2004;Hamilton et al, 2007). Finally, CD8 þ tumour infiltrating lymphocytes (TILs) have been linked to improved survival in colorectal cancer patients (Chiba et al, 2004;Galon et al, 2006).…”

mentioning

confidence: 99%

Two-marker protein profile predicts poor prognosis in patients with early rectal cancer

et al. 2008

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The aim of this study was to establish an immunohistochemical protein profile to complement preoperative staging and identify rectal cancer patients at high-risk of adverse outcome. Immunohistochemistry was performed on a tissue microarray including 482 rectal cancers for APAF-1, EphB2, MST1, Ki67, p53, RHAMM, RKIP and CD8 þ tumour infiltrating lymphocytes (TILs). After resampling of the data and multivariable analysis, the most reproducible markers were combined and prognosis evaluated as stratified by pT and pN status. In multivariable analysis, only positive RHAMM (Po0.001; HR ¼ 1.94 (1.44 -2.61)) and loss of CD8 þ TILs (P ¼ 0.006; HR ¼ 0.63 (0.45 -0.88)) were independent prognostic factors. The 5-year cancer-specific survival rate for RHAMM þ /TILÀ patients was 30% (95% CI 21 -40%) compared to 76% (95% CI: 66 -84%) for RHAMMÀ/TIL þ patients (Po0.001). The 5-year cancerspecific survival of T1/T2/RHAMM þ /TILÀ patients was 48% (20 -72%) and significantly worse compared to T3/T4/RHAMMÀ/ TIL þ patients (71% 95% CI 56 -82%); P ¼ 0.039). Stratifying by nodal status, only N þ /RHAMM þ /TILÀ patients demonstrated a significantly worse prognosis than N0/RHAMM þ /TILÀ patients (P ¼ 0.005). Loss of CD8 þ TILs was predictive of local recurrence in RHAMM þ tumours (P ¼ 0.009) only. RHAMM and CD8 þ TILs may assist in identifying early stage rectal cancer patients facing a particularly poor prognosis and who may derive a benefit from preoperative therapy.

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RHAMM expression and isoform balance predict aggressive disease and poor survival in multiple myeloma

Abstract: Multiple myeloma (MM) plasma cells (PCs

Cited by 96 publications

References 32 publications

Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance

Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance

Rab15 expression correlates with retinoic acid-induced differentiation of neuroblastoma cells

Two-marker protein profile predicts poor prognosis in patients with early rectal cancer

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