Isotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular Resolution

被引：28

作者：

Edgar, Landon J. ^{[1
]}

Vellanki, Ravi N. ^{[2
,3
,4
]}

Mckee, Trevor D. ^{[2
,3
,4
]}

Hedley, David ^{[2
,3
,4
]}

Wouters, Bradly G. ^{[2
,3
,4
]}

Nitz, Mark ^{[1
]}

机构：

[1] Univ Toronto, Dept Chem, 80 St George St, Toronto, ON M5S 3H6, Canada

[2] Univ Hlth Network, Dept Radiat Oncol, 101 Coll St, Toronto, ON M5G 1L7, Canada

[3] Univ Hlth Network, Dept Med Biophys, 101 Coll St, Toronto, ON M5G 1L7, Canada

[4] Univ Hlth Network, STTARR Innovaton Ctr, Princess Margaret Canc Ctr, 101 Coll St, Toronto, ON M5G 1L7, Canada

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2016年 / 55卷 / 42期

基金：

加拿大自然科学与工程研究理事会;

关键词：

activity-based probes; cellular hypoxia; dynamic biology; mass spectrometry; tellurium; TUMOR; CELLS; TISSUES;

D O I：

10.1002/anie.201607483

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Changes in the oxygenation state of microenvironments within solid tumors are associated with the development of aggressive cancer phenotypes. Factors that influence cellular hypoxia have been characterized; however, methods for measuring the dynamics of oxygenation at a cellular level in vivo have been elusive. We report a series of tellurium-containing isotopologous probes for cellular hypoxia compatible with mass cytometry (MC)-technology that allows for highly parametric interrogation of single cells based on atomic mass spectrometry. Sequential labeling with the isotopologous probes (SLIP) in pancreatic tumor xenograft models revealed changes in cellular oxygenation over time which correlated with the distance from vasculature, the proliferation of cell populations, and proximity to necrosis. SLIP allows for capture of spatial and temporal dynamics in vivo using enzyme activated probes.

引用

页码：13159 / 13163

页数：5

共 20 条

[1]

Bennewith KL, 2002, CANCER RES, V62, P6827

[2] KINETICS AND MECHANISM OF THE DECOMPOSITION IN AQUEOUS-SOLUTIONS OF 2-(HYDROXYAMINO)IMIDAZOLES [J].

BOLTON, JL ;

MCCLELLAND, RA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (21) :8172-8181

[3] Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response [J].

Dewhirst, Mark W. ;

Cao, Yiting ;

Moeller, Benjamin .

NATURE REVIEWS CANCER, 2008, 8 (06) :425-437

[4]

Edgar L.J., 2014, Angew. Chem. Int. Edit, V126, P11657

[5] Identification of Hypoxic Cells Using an Organotellurium Tag Compatible with Mass Cytometry [J].

Edgar, Landon J. ;

Vellanki, Ravi N. ;

Halupa, Adrienne ;

Hedley, David ;

Wouters, Bradly G. ;

Nitz, Mark .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2014, 53 (43) :11473-11477

[6]

Giesen C, 2014, NAT METHODS, V11, P417, DOI [10.1038/NMETH.2869, 10.1038/nmeth.2869]

[7]

Hodgkiss RJ, 1998, ANTI-CANCER DRUG DES, V13, P687

[8] DIRECT EVIDENCE THAT HYDRALAZINE CAN INDUCE HYPOXIA IN BOTH TRANSPLANTED AND SPONTANEOUS MURINE TUMORS [J].

HORSMAN, MR ;

NORDSMARK, M ;

HOYER, M ;

OVERGAARD, J .

BRITISH JOURNAL OF CANCER, 1995, 72 (06) :1474-1478

[9]

Koch CJ, 2002, METHOD ENZYMOL, V352, P3

[10] Preconditioning of the tumor vasculature and tumor cells by intermittent hypoxia:: Implications for anticancer therapies [J].

Martinive, Philippe ;

Defresne, Florence ;

Bouzin, Caroline ;

Saliez, Julie ;

Lair, Florence ;

Gregoire, Vincent ;

Michiels, Carine ;

Dessy, Chantal ;

Feron, Olivier .

CANCER RESEARCH, 2006, 66 (24) :11736-11744

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