PMID- 12880957
OWN - NLM
STAT- MEDLINE
DCOM- 20030923
LR  - 20190720
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 197
IP  - 1-2
DP  - 2003 Jul 18
TI  - A role for distinct cell types in determining malignancy in human neuroblastoma 
      cell lines and tumors.
PG  - 35-9
AB  - Human neuroblastoma arises from the developing neural crest. Tumors are 
      categorized clinically by their location, age at diagnosis, spread/metastasis, 
      and degree of cellular maturation and heterogeneity. Our long-term studies have 
      shown the presence in human neuroblastoma cell lines of three distinct cell 
      types: I-type stem cells, N-type neuroblastic/neuroendocrine precursors, and 
      S-type Schwannian/melanoblastic precursors. These distinct cell types can 
      differentiate predictably along specific neural crest lineages in response to 
      particular morphogens. As assessed by tumor formation in nude mice and 
      anchorage-independent growth in soft agar, I-type stem cells are significantly 
      more malignant than either N- or S-type cells. Recent research shows that three 
      similar cell types are also present in human neuroblastoma tumors. Using 
      immunocytochemical, laser-capture microdissection, or short-term culture methods 
      to identify cell types in tumors of different stages and/or different outcomes, 
      these studies have shown that (1) all tumors contain neuroblasts in various 
      differentiation states; (2) presumptive I-type stem cells are present in tumors 
      of all stages; and (3) stromal cells may be tumor-derived, i.e. S-type cells, as 
      well as of normal origin. More importantly, there is a higher incidence of I-type 
      cells in tumors that progress, consistent with the high malignant potential of 
      this cell type in vitro. A better understanding of the cause and consequences of 
      cellular heterogeneity of human neuroblastoma tumors is an important prerequisite 
      to the development of more effective therapies for this often fatal disease.
FAU - Ross, Robert A
AU  - Ross RA
AD  - Laboratory of Neurobiology, Department of Biological Sciences, Fordham 
      University, 441 E. Fordham Road, Bronx, NY 10458, USA. rross@fordham.edu
FAU - Biedler, June L
AU  - Biedler JL
FAU - Spengler, Barbara A
AU  - Spengler BA
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cell Transformation, Neoplastic
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Incidence
MH  - Neoplasm Proteins/metabolism
MH  - Nervous System Neoplasms/metabolism/*pathology
MH  - Neuroblastoma/metabolism/*pathology
MH  - Tumor Cells, Cultured
RF  - 14
EDAT- 2003/07/26 05:00
MHDA- 2003/09/25 05:00
CRDT- 2003/07/26 05:00
PHST- 2003/07/26 05:00 [pubmed]
PHST- 2003/09/25 05:00 [medline]
PHST- 2003/07/26 05:00 [entrez]
AID - S030438350300079X [pii]
AID - 10.1016/s0304-3835(03)00079-x [doi]
PST - ppublish
SO  - Cancer Lett. 2003 Jul 18;197(1-2):35-9. doi: 10.1016/s0304-3835(03)00079-x.