MUC1 Story: Great Expectations, Disappointments and the Renaissance

In the course of studying human mucin MUC1, the attitude towards this molecule has been changing time and again. Initially, the list of presumable functions of MUC1 was restricted to protecting and lubricating epithelium. To date, it is assumed to play an important role in cell signaling as well as in all stages of oncogenesis, from malignant cell transformation to tumor dissemination. The story of MUC1 is full of hopes and disappointments. However, the scientific interest to MUC1 has never waned, and the more profoundly it has been investigated, the clearer its hidden potential turned to be disclosed. The therapeutic potential of mucin MUC1 has already been noted by various scientific groups at the early stages of research. Over forty years ago, the first insights into MUC1 functions became a strong ground for considering this molecule as potential target for anticancer therapy. Therefore, this direction of research has always been of particular interest and practical importance. More than 200 papers on MUC1 were published in 2016; the majority of them are dedicated to MUC1-related anticancer diagnostics and therapeutics. Here we review the history of MUC1 studies from the very first attempts to reveal its functions to the ongoing renaissance.

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Hodgkin Lymphoma

10.1093/oso/9780190676827.003.0026 ◽

2018 ◽

Cited By ~ 1

Author(s):

Henrik Hjalgrim ◽

Mads Melbye ◽

Pagona Lagiou

Keyword(s):

Natural History ◽

Hodgkin Lymphoma ◽

Cell Transformation ◽

Malignant Cell ◽

Future Research ◽

Barr Virus ◽

History Of ◽

Epstein Barr ◽

Malignant Cell Transformation

The descriptive epidemiology of Hodgkin lymphoma (HL) has demonstrated marked variation by age, sex, social class, and time, strongly suggesting both a role of environmental factors and the existence of etiologically diverse HL subtypes. There is increasing evidence that Epstein Barr virus (EBV)–positive and EBV-negative classical HLs define two variants with separate etiologies. The risk for both increases with family history, whereas immune dysfunction and infectious mononucleosis have been implicated in EBV-positive HL risk only. Despite being the less common of the two, the natural history of EBV-positive HL is currently the best understood, both with respect to how EBV may contribute to malignant cell transformation and in relation to constitutional and environmental risk factors. Meanwhile, the understanding of the natural history of EBV-negative HL is meager. Future research for EBV-negative HL is expected to focus on its presumed infectious etiology, for which there are currently no strong candidates.

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Synthesis and in vitro characterization of the genotoxic, mutagenic and cell-transforming potential of nitrosylated heme

Archives of Toxicology ◽

10.1007/s00204-020-02846-8 ◽

2020 ◽

Vol 94 (11) ◽

pp. 3911-3927 ◽

Cited By ~ 1

Author(s):

Tina Kostka ◽

Jörg Fohrer ◽

Claudia Guigas ◽

Karlis Briviba ◽

Nina Seiwert ◽

...

Keyword(s):

Cell Transformation ◽

Malignant Cell ◽

Red Meat ◽

Colorectal Carcinogenesis ◽

In Vivo Studies ◽

Processed Meat ◽

Cell Transforming ◽

Malignant Cell Transformation

Abstract Data from epidemiological studies suggest that consumption of red and processed meat is a factor contributing to colorectal carcinogenesis. Red meat contains high amounts of heme, which in turn can be converted to its nitrosylated form, NO-heme, when adding nitrite-containing curing salt to meat. NO-heme might contribute to colorectal cancer formation by causing gene mutations and could thereby be responsible for the association of (processed) red meat consumption with intestinal cancer. Up to now, neither in vitro nor in vivo studies characterizing the mutagenic and cell transforming potential of NO-heme have been published due to the fact that the pure compound is not readily available. Therefore, in the present study, an already existing synthesis protocol was modified to yield, for the first time, purified NO-heme. Thereafter, newly synthesized NO-heme was chemically characterized and used in various in vitro approaches at dietary concentrations to determine whether it can lead to DNA damage and malignant cell transformation. While NO-heme led to a significant dose-dependent increase in the number of DNA strand breaks in the comet assay and was mutagenic in the HPRT assay, this compound tested negative in the Ames test and failed to induce malignant cell transformation in the BALB/c 3T3 cell transformation assay. Interestingly, the non-nitrosylated heme control showed similar effects, but was additionally able to induce malignant transformation in BALB/c 3T3 murine fibroblasts. Taken together, these results suggest that it is the heme molecule rather than the NO moiety which is involved in driving red meat-associated carcinogenesis.

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