Neural crest derived progenitor cells contribute to tumor stroma and aggressiveness in stage 4/M neuroblastoma

نویسندگان

  • Pedro Linares-Clemente
  • Diana Aguilar-Morante
  • Ismael Rodríguez-Prieto
  • Gema Ramírez
  • Carmen de Torres
  • Vicente Santamaría
  • Diego Pascual-Vaca
  • Ana Colmenero-Repiso
  • Francisco M. Vega
  • Jaume Mora
  • Rosa Cabello
  • Catalina Márquez
  • Eloy Rivas
  • Ricardo Pardal
چکیده

Pediatric tumors arise upon oncogenic transformation of stem/progenitor cells during embryonic development. Given this scenario, the existence of non-tumorigenic stem cells included within the aberrant tumoral niche, with a potential role in tumor biology, is an intriguing and unstudied possibility. Here, we describe the presence and function of non-tumorigenic neural crest-derived progenitor cells in aggressive neuroblastoma (NB) tumors. These cells differentiate into neural crest typical mesectodermal derivatives, giving rise to tumor stroma and promoting proliferation and tumor aggressiveness. Furthermore, an analysis of gene expression profiles in stage 4/M NB revealed a neural crest stem cell (NCSC) gene signature that was associated to stromal phenotype and high probability of relapse. Thus, this NCSC gene expression signature could be used in prognosis to improve stratification of stage 4/M NB tumors. Our results might facilitate the design of new therapies by targeting NCSCs and their contribution to tumor stroma.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

TRPM7 maintains progenitor-like features of neuroblastoma cells: implications for metastasis formation

Neuroblastoma is an embryonal tumor derived from poorly differentiated neural crest cells. Current research is aimed at identifying the molecular mechanisms that maintain the progenitor state of neuroblastoma cells and to develop novel therapeutic strategies that induce neuroblastoma cell differentiation. Mechanisms controlling neural crest development are typically dysregulated during neurobla...

متن کامل

CD57high Neuroblastoma Cells Have Aggressive Attributes Ex Situ and an Undifferentiated Phenotype in Patients

BACKGROUND Neuroblastoma is thought to originate from neural crest-derived cells. CD57 defines migratory neural crest cells in normal development and is expressed in neuroblastoma. METHODOLOGY AND PRINCIPAL FINDINGS We investigated the role of CD57 expression in neuroblastoma cells ex situ and in situ. Compared to CD57(low) U-NB1 neuroblastoma cells, CD57(high) cells developed tumors with dec...

متن کامل

RD3 loss dictates high-risk aggressive neuroblastoma and poor clinical outcomes

Clinical outcomes for high-risk neuroblastoma patients remains poor, with only 40-50% 5-Year overall survival (OS) and <10% long-term survival. The ongoing acquisition of genetic/molecular rearrangements in undifferentiated neural crest cells may endorse neuroblastoma progression. This study recognized the loss of Retinal Degeneration protein 3, RD3 in aggressive neuroblastoma, and identified i...

متن کامل

EYA1 expression and subcellular localization in neuroblastoma and its association with prognostic markers

Neuroblastoma, the most frequently occurring extracranial solid tumor of childhood, arises from neural crest-derived cells that are arrested at an early stage of differentiation in the developing sympathetic nervous system. There is an urgent need to identify clinically relevant biomarkers for better prognosis and treatment of this aggressive malignancy. Eyes Absent 1 (EYA1) is an essential tra...

متن کامل

FOXD3 is a novel tumor suppressor that affects growth, invasion, metastasis and angiogenesis of neuroblastoma

The transcription factor forkhead box D3 (FOXD3) plays a crucial role in the development of neural crest cells. However, the function and underlying mechanisms of FOXD3 in the progression of neuroblastoma (NB), an embryonal tumor that is derived from the neural crest, still remain largely unknown. Here, we report that FOXD3 is an important oncosuppressor of NB tumorigenicity and aggressiveness....

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017