Cet article passe en revue les études concernant les effets du plomb et du cadmium sur le système immunitaire et la progression tumorale

Effects of lead and cadmium on the immune system and cancer progression

Ebrahimi, Maryam ; Khalili, Neda ; Razi, Sepideh ; Keshavarz-Fathi, Mahsa ; Khalili, Nastaran ; Rezaei, Nima

In our daily life, we are surrounded by harmful pollutants, including heavy metals that are not visible in the macroscopic view easily. Heavy metals can disrupt different aspects of human health, such as the immune system which has gained a lot of attention in recent decades. This had led to its rapid progression and new insights into its alterations in different diseases especially cancer. Heavy metals are non-biodegradable materials that exist in different parts of the food cycle, such as [...]

Menée à partir de données génomiques du projet "ICGC/TCGA Pan-Cancer Analysis of Whole Genomes" portant sur 2 500 tumeurs, cette étude analyse les caractéristiques des mutations passagères ainsi que leurs effets sur la tumorigenèse et la progression tumorale

Passenger Mutations in More Than 2,500 Cancer Genomes: Overall Molecular Functional Impact and Consequences

Kumar, Sushant ; Warrell, Jonathan ; Li, Shantao ; McGillivray, Patrick D. ; Meyerson, William ; Salichos, Leonidas ; Harmanci, Arif ; Martinez-Fundichely, Alexander ; Chan, Calvin W. Y. ; Nielsen, Morten Muhlig ; Lochovsky, Lucas ; Zhang, Yan ; Li, Xiaotong ; Lou, Shaoke ; Pedersen, Jakob Skou ; Herrmann, Carl ; Getz, Gad ; Khurana, Ekta ; Gerstein, Mark B.

The dichotomous model of ?drivers? and ?passengers? in cancer posits that only a few mutations in a tumor strongly affect its progression, with the remaining ones being inconsequential. Here, we leveraged the comprehensive variant dataset from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) project to demonstrate that?in addition to the dichotomy of high- and low-impact variants?there is a third group of medium-impact putative passengers. Moreover, we also found that molecular impact [...]

Menée in vitro et à l'aide d'un modèle murin de leucémie myéloïde chronique, cette étude analyse le rôle de la réponse immunitaire innée dans la récidive de la maladie ou la crise blastique

Investigating the role of the innate immune response in relapse or blast crisis in chronic myeloid leukemia

Huang, Weiqi ; Liu, Bin ; Eklund, Elizabeth A.

Chronic myeloid leukemia (CML) is characterized by expression of the tyrosine kinase oncogene, Bcr–abl. Tyrosine kinase inhibitors (TKI) induce prolonged remission in CML, and therapy discontinuation is an accepted approach to patients with reduction in Bcr–abl transcripts of four logs or greater. Half such individuals sustain a therapy free remission, but molecular mechanisms predicting relapse are undefined. We found relative calpain inhibition in CML cells with stabilization of calpain [...]

Menée sur des lignées cellulaires de lymphome hodgkinien, cette étude met en évidence le transfert par trogocytose de protéines PD-L1/L2 de cellules cancéreuses vers la surface des monocytes

PD-L1/L2 protein levels rapidly increase on monocytes via trogocytosis from tumor cells in classical Hodgkin lymphoma

Kawashima, Masaharu ; Carreras, Joaquim ; Higuchi, Hiroshi ; Kotaki, Ryutaro ; Hoshina, Takahiro ; Okuyama, Kazuki ; Suzuki, Naoto ; Kakizaki, Masatoshi ; Miyatake, Yuji ; Ando, Kiyoshi ; Nakayama, Masafumi ; Umezu, Shinjiro ; Horie, Ryouichi ; Higuchi, Yuriko ; Katagiri, Koko ; Goyama, Susumu ; Kitamura, Toshio ; Chamoto, Kenji ; Yano, Shingo ; Nakamura, Naoya ; Kotani, Ai

In classical Hodgkin lymphoma (cHL)—characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells—tumor-associated macrophages (TAMs) play a pivotal role in tumor formation. However, the significance of direct contact between HRS cells and TAMs has not been elucidated. HRS cells and TAMs are known to express PD-L1, which leads to PD-1+ CD4+ T cell exhaustion in cHL. Here, we found that PD-L1/L2 expression was elevated in monocytes co-cultured with HRS cells within 1 h, but not in [...]

Menée à partir du séquençage de l'ensemble de l'exome de différentes régions de tumeurs primitives et de métastases provenant de six patientes atteintes d'un carcinome ovarien de haut grade, cette étude analyse l'hétérogénéité génétique et l'évolution clonale des tumeurs primitives et de leurs métastases

Genetic heterogeneity and evolutionary history of high-grade ovarian carcinoma and matched distant metastases

Masoodi, Tariq ; Siraj, Sarah ; Siraj, Abdul K. ; Azam, Saud ; Qadri, Zeeshan ; Parvathareddy, Sandeep K. ; Tulbah, Asma ; Al-Dayel, Fouad ; AlHusaini, Hamed ; AlOmar, Osama ; Al-Badawi, Ismail A. ; Alkuraya, Fowzan S. ; Al-Kuraya, Khawla S.

Background : High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian carcinoma, associated with poor clinical outcome and metastatic disease. Although metastatic processes are becoming more understandable, the genomic landscape and metastatic progression in HGSOC has not been elucidated. Methods : Multi-region whole-exome sequencing was performed on HGSOC primary tumours and their metastases (n = 33 tumour regions) from six patients. The resulting somatic variants were [...]

Menée à l'aide de 13 lignées cellulaires de cancer du côlon présentant une trisomie, cette étude démontre que le gain d'un chromosome peut aussi bien favoriser que supprimer le processus métastatique

Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer

Vasudevan, Anand ; Baruah, Prasamit S. ; Smith, Joan C. ; Wang, Zihua ; Sayles, Nicole M. ; Andrews, Peter ; Kendall, Jude ; Leu, Justin ; Chunduri, Narendra Kumar ; Levy, Dan ; Wigler, Michael ; Storchova, Zuzana ; Sheltzer, Jason M.

High levels of cancer aneuploidy are frequently associated with poor prognosis. To examine the relationship between aneuploidy and cancer progression, we analyzed a series of congenic cell lines that harbor single extra chromosomes. We found that across 13 different trisomic cell lines, 12 trisomies suppressed invasiveness or were largely neutral, while a single trisomy increased metastatic behavior by triggering a partial epithelial-mesenchymal transition. In contrast, we discovered that [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel les cellules épithéliales pulmonaires régulent la dissémination des cellules mammaires cancéreuses ayant migré vers le poumon en induisant l'expression de la protéine Sfrp2 dans ces mêmes cellules

Crosstalk with lung epithelial cells regulates Sfrp2-mediated latency in breast cancer dissemination

Montagner, Marco ; Bhome, Rahul ; Hooper, Steven ; Chakravarty, Probir ; Qin, Xiao ; Sufi, Jahangir ; Bhargava, Ajay ; Ratcliffe, Colin D. H. ; Naito, Yutaka ; Pocaterra, Arianna ; Tape, Christopher J. ; Sahai, Erik

The process of metastasis is complex1. In breast cancer, there are frequently long time intervals between cells leaving the primary tumour and growth of overt metastases2,3. Reasons for disease indolence and subsequent transition back to aggressive growth include interactions with myeloid and fibroblastic cells in the tumour microenvironment and ongoing immune surveillance4–6. However, the signals that cause actively growing cells to enter an indolent state, thereby enabling them to survive for [...]

Menée à l'aide de lignées cellulaires d'épithélium bronchique humain et de cancer du poumon non à petites cellules, cette étude met en évidence le rôle de l'architecture du cytosquelette d'actomyosine dans la régulation de la glycolyse

Mechanical regulation of glycolysis via cytoskeleton architecture

Park, Jin Suk ; Burckhardt, Christoph J. ; Lazcano, Rossana ; Solis, Luisa M. ; Isogai, Tadamoto ; Li, Linqing ; Chen, Christopher S. ; Gao, Boning ; Minna, John D. ; Bachoo, Robert ; DeBerardinis, Ralph J. ; Danuser, Gaudenz

The mechanics of the cellular microenvironment continuously modulates cell functions such as growth, survival, apoptosis, differentiation and morphogenesis via cytoskeletal remodelling and actomyosin contractility1–3. Although all of these processes consume energy4,5, it is unknown whether and how cells adapt their metabolic activity to variable mechanical cues. Here we report that the transfer of human bronchial epithelial cells from stiff to soft substrates causes a downregulation of [...]