Alterations in cancer stem-cell marker CD44 expression predict oncologic outcome in soft-tissue sarcomas

Henderson, T. O.; Chen, Mingyi; Darrow, Morgan A.; Li, Chin Shang; Chiu, Chi Lu; Monjazeb, Arta M.; Murphy, William J.; Canter, Robert J.

doi:10.1016/j.jss.2017.11.016

Cited by 19 publications

(14 citation statements)

References 50 publications

(54 reference statements)

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“…CD44 is involved in cellular differentiation and migration, and abnormal expression of CD44 in cancer and sarcoma cells may promote invasion and lead to local recurrence and distant metastases (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). In the present study, enhanced expression of CD44s was found to be a poor prognostic factor for local recurrence.…”

Section: Discussionsupporting

confidence: 51%

“…Conflicting results regarding the expression of CD44 in sarcoma have been reported. Although poor prognosis is associated with the overexpression of CD44v6, a variant form of CD44, discrepant results have been reported for CD44s (15)(16)(17)(18)(19)(20)(21)(22)(27)(28)(29)(30)(31)(32)(33)(34). Some studies of various types of soft tissue sarcoma have reported that high expression of CD44, including both standard and unknown forms, is likely to have adverse effects on prognosis, distant metastasis, and local recurrence, whereas other studies have reported good prognosis in patients with increased CD44s expression (15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

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Prognostic Impact of CD44 Expression in Patients With Myxofibrosarcoma

Tsuchie

Emori

Miyakoshi

et al. 2019

In Vivo

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Background/Aim: Abnormal expression of CD44 may promote cancer invasion. However, a limited number of studies have investigated the expression of CD44 in soft tissue sarcoma such as myxofibrosarcoma. We evaluated the relationship between expression of the standard form of CD44 (CD44s) and the clinical course of myxofibrosarcoma. Materials and Methods: Forty-four myxofibrosarcoma patients were retrospectively enrolled. Patient information including the proportion of CD44s-positive cells was collected, and multivariate analyses were conducted to determine the relationship between CD44s expression and clinicopathological factors. Results: Although CD44s did not affect prognosis, multivariate analysis indicated that high expression of CD44s predicted poor event-free survival (p=0.004) and local recurrence (p=0.049). CD44s expression was not associated with the occurrence of distant metastasis but was significantly higher in those with lung metastasis (p=0.044). Conclusion: Increased expression of CD44s predicted poor event-free survival and local recurrence and was observed in myxofibrosarcoma patients with lung metastasis. Myxofibrosarcoma is a common soft-tissue sarcoma found in the extremities of older adults and accounts for approximately 20% of all soft-tissue sarcomas (1). Although complete surgical resection is the standard treatment, negative margins are difficult to obtain, since myxofibrosarcoma has an unusual infiltrative growth pattern along fascial plane (2). Therefore, myxofibrosarcoma outcomes are characterized by high local recurrence rates (15 to 57%), leading to poor overall survival (3-8). In addition, distant metastases of myxofibrosarcoma are common. In particular, lung metastasis greatly affects prognosis (9). Although some factors associated with local recurrence, such as resection with positive or close margins and bone and joint involvement, have been examined in many studies, little is known regarding pre-existing factors that facilitate local recurrence or distant metastasis (3-5, 7, 8). Cell-cell and cell-matrix interactions are essential for normal cell growth and differentiation, and a variety of adhesion molecules participate in these interactions, including the hyaluronic acid binding transmembrane glycoprotein CD44. The standard form of CD44 (CD44s) and its variants are ubiquitously expressed on all cell types, where they act as receptors for hyaluronic acid. CD44 plays various roles and is involved in cellular differentiation, cellular migration, and cell-cell contact (10). Therefore, abnormal expression of CD44 in cancer and sarcoma cells may promote invasion and lead to local recurrence and distant metastases, ultimately affecting prognosis. Previous studies have reported the association between abnormal expression of CD44 and tumor growth or more aggressive behavior in various cancers, such as breast, gastric, colorectal, and lung cancer (11-14). However, relatively few studies have investigated the expression of CD44 in soft tissue sarcoma, with even fewer reports on myxofibrosar...

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of CD44 Expression in Patients With Myxofibrosarcoma

Tsuchie

Emori

Miyakoshi

et al. 2019

In Vivo

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“…Yet, its potential value to discriminate CSCs sub-populations in STS is very limited and it has been reported that this cell surface marker could not be a useful tool to isolate CSCs in STS [31]. Nonetheless, elevated levels of CD44 expression were associated with worse outcome in STS; however, and since CD44 has pleotropic cellular functions, this association might be unrelated to the stem-like behavior of CD44+ STS cells [32].…”

Section: Cd44mentioning

confidence: 99%

“…Several studies have linked the expression of CD44, one of the HA receptors, with the CSC phenotype, thus converting this protein in a potential therapeutic target [106]. High CD44 expression was associated with worse outcome in STS [32]. Current therapeutic approaches include neutralizing antibody, peptide mimetic, aptamers, natural compounds suppressing CD44 expression, targeting HA by bio-conjugates and nanoparticles, CD44 decoys, and HA oligomers.…”

Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Cancer Stem Cells in Soft-Tissue Sarcomas

Martínez-Delgado

Lacerenza

Obrador‐Hevia

et al. 2020

Cells

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Soft tissue sarcomas (STS) are a rare group of mesenchymal solid tumors with heterogeneous genetic profiles and clinical features. Systemic chemotherapy is the backbone treatment for advanced STS; however, STS frequently acquire resistance to standard therapies, which highlights the need to improve treatments and identify novel therapeutic targets. Increases in the knowledge of the molecular pathways that drive sarcomas have brought to light different molecular alterations that cause tumor initiation and progression. These findings have triggered a breakthrough of targeted therapies that are being assessed in clinical trials. Cancer stem cells (CSCs) exhibit mesenchymal stem cell (MSC) features and represent a subpopulation of tumor cells that play an important role in tumor progression, chemotherapy resistance, recurrence and metastasis. In fact, CSCs phenotypes have been identified in sarcomas, allied to drug resistance and tumorigenesis. Herein, we will review the published evidence of CSCs in STS, discussing the molecular characteristic of CSCs, the commonly used isolation techniques and the new possibilities of targeting CSCs as a way to improve STS treatment and consequently patient outcome.

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“…The CSCs within tumor bulk display the capacity to self-renew, differentiate, and give rise to a new tumor (Visvader and Lindeman 2012 ). Recently, lots of surface markers of CSCs have been identified, including CD133, CD13, CD24, ALDH1A1, CD44, and so on (Henderson et al 2018 ; Li et al 2018 ; Marotta et al 2011 ; Organista-Nava et al 2014 ; Yang et al 2014 ). It is still a general strategy to isolate CSCs by FACS and to examine their biological features.…”

Section: Biological Characteristics and Study Strategies Of Cscsmentioning

confidence: 99%

Cancer stem cells and tumorigenesis

Zhu

Fan

2018

Biophys Rep

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Cancer is one of the most serious diseases all over the world, and the cancer stem cell (CSC) model accounts for tumor initiation, metastasis, drug resistance, and relapse. The CSCs within tumor bulk have the capacity to self-renew, differentiate, and give rise to a new tumor. The self-renewal of CSCs is precisely regulated by various modulators, including Wnt/β-catenin signaling, Notch signaling, Hedgehog signaling, transcription factors, chromatin remodeling complexes, and non-coding RNAs. CSCs reside in their niches that are also involved in the self-renewal maintenance of CSCs and protection of CSCs from chemotherapy, radiotherapy, and even endogenous damages. Moreover, CSCs can also remodel their niches to initiate tumorigenesis. The mutual interactions between CSCs and their niches play a critical role in the regulation of CSC self-renewal and tumorigenesis as well. Many surface markers of CSCs have been identified, and these markers become first choices for CSC targeting. Due to heterogeneity and plasticity, targeting CSCs is still a big challenge for tumor elimination. In this review, we summarize recent progresses on the biological features of CSCs and targeting strategies against CSCs.

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Alterations in cancer stem-cell marker CD44 expression predict oncologic outcome in soft-tissue sarcomas

Abstract: Institutional and national TCGA data show the association of elevated baseline CD44 expression with worse STS outcomes. Further study of CD44 as a possible novel STS biomarker appears indicated.

Cited by 19 publications

References 50 publications

Prognostic Impact of CD44 Expression in Patients With Myxofibrosarcoma

Prognostic Impact of CD44 Expression in Patients With Myxofibrosarcoma

Cancer Stem Cells in Soft-Tissue Sarcomas

Cancer stem cells and tumorigenesis

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