scholarly journals Tissue architectural cues drive organ targeting of human tumor cells in zebrafish

2017 ◽  
Author(s):  
Colin D. Paul ◽  
Kevin Bishop ◽  
Alexus Devine ◽  
Elliott L. Paine ◽  
Jack R. Staunton ◽  
...  

ABSTRACTSites of metastasis are non-random, with certain types of cancers showing organ preference during distal colonization. Using multiple brain- and bone marrow-seeking human and murine breast cancer subclones, we determined that tumor cells that home to specific murine organs (brain and bone marrow) ultimately colonized analogous tissues (brain and caudal vein plexus [CVP]) in larval zebrafish. We then exploited the zebrafish model to delineate factors leading to differential cell homing and extravasation. Bone marrow-tropic clones showed higher expression of integrins and focal adhesions associated with mechanosensing machinery than brain-tropic clones and were more sensitive to vessel topography during extravasation. Knockdown of β1 integrin reduced extravasation and redistributed organ targeting from disordered vessels in the CVP to the brain. Our results show that organ selectivity is driven by topography- and cell type-dependent extravasation at the tumor-endothelial interface in the larval zebrafish and provide important insights into the early stages of metastasis.

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4677-4680 ◽  
Author(s):  
Katy J. McCann ◽  
Margaret Ashton-Key ◽  
KellyAnn Smith ◽  
Freda K. Stevenson ◽  
Christian H. Ottensmeier

Abstract Primary central nervous system (CNS) lymphoma is an aggressive B-cell tumor that is defined clinically by the absence of systemic disease. We have used immunoglobulin variable (V)–gene analysis to identify tumor cells at the CNS site in 12 cases and to probe the involvement of peripheral tissues in 3 patients. Clonal tracking revealed tumor cells in the bone marrow and/or blood for 3 of 3 cases, with evidence for increased V-gene mutational activity at peripheral sites. In 2 of 3 cases, intraclonal variant analysis revealed identity with the brain biopsy but detected additional variants unique to extracerebral sites. These findings suggest that peripheral tumor cells can undergo separate development locally with no reentry into the brain. Primary CNS lymphoma appears to have both CNS-specific and systemic components with limited interchange. The more malignant behavior of tumor cells in the CNS suggests either a local environmental influence or a less malignant phenotype of the peripheral clone.


2011 ◽  
Author(s):  
Sreeraj G. Pillai ◽  
Shunqiang Li ◽  
Chidananda Mudalagiriyappa ◽  
Mark A. Watson ◽  
Timothy P. Fleming ◽  
...  

1990 ◽  
Vol 82 (5) ◽  
pp. 408-412 ◽  
Author(s):  
I. KjOnniksen ◽  
J. M. Nesland ◽  
A. Pihl ◽  
O Fodstad

Author(s):  
C. N. Sun ◽  
C. Araoz ◽  
H. J. White

The ultrastructure of a cerebral primitive neuroectodermal tumor has been reported previously. In the present case, we will present some unusual previously unreported membranous structures and alterations in the cytoplasm and nucleus of the tumor cells.Specimens were cut into small pieces about 1 mm3 and immediately fixed in 4% glutaraldehyde in phosphate buffer for two hours, then post-fixed in 1% buffered osmium tetroxide for one hour. After dehydration, tissues were embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate.In the cytoplasm of the tumor cells, we found paired cisternae (Fig. 1) and annulate lamellae (Fig. 2) noting that the annulate lamellae were sometimes associated with the outer nuclear envelope (Fig. 3). These membranous structures have been reported in other tumor cells. In our case, mitochondrial to nuclear envelope fusions were often noted (Fig. 4). Although this phenomenon was reported in an oncocytoma, their frequency in the present study is quite striking.


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