Single cell analysis reveals a pro cancerous growth signature induced by circulating tumor cells in lung endothelial cells

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School of Electrical Engineering | Bachelor's thesis
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Date

2025-12-08

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Bioinformation Technology

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Bachelor's Programme in Electrical Engineering
Sähkötekniikan kandidaattiohjelma
Kandidatprogrammet i elektroteknik

Language

en

Pages

16

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Abstract

Circulating tumor cells (CTCs) exit the blood vessels in capillaries to form micrometastasis. We recently found that CTCs rapidly reprogram ECs in lung capillaries during lung etastatic colonization. Here, I analyse single-cell RNA sequencing (scRNA-seq) data from reactive capillary endothelial cells (rCap) in mouse lungs in response to CTCs. I use scRNAseq data of ECs from mouse lung vasculature 6 h after injection of melanoma cells into mouse circulation and corresponding data from control samples. The analysis showed that rCap cells constitute at least two subclusters which express genes with distinct functions: Pim3+ cluster expressed genes with potential vascular protective function, whereas Inhbb+ cluster expressed genes previously linked to cancer progression. Pathway analysis shows higher expression of Myc target genes in Inhbb+ cluster and higher expression of some target genes of mutant KRAS signaling pathway. Inhbb+ cluster also had higher expressions of Myc itself as well as Erk and very low expression of Erf, which is phosphorylated by Erk and, in turns, represses the expression of Myc. On the other hand, Erf was highly expressed in Pim3+ cluster, in consistence with low Myc gene signature. These findings are consistent with the cascade that occurs in some cancer cells because of KRAS mutation, in which KRAS mutation activates ERK, which leads to the expression of Myc. The result, if confirmed experimentally, can help to understand the function of rCap cells in shaping the lung capillary endothelium during micrometastasis initiation and can contribute to development of drugs to prevent metastasis and cancer recurrence through the inhibition of micrometastasis or biomarkers of early metastatic lesions.

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Supervisor

Turunen, Markus

Thesis advisor

Palva, Lauri
Saharinen, Pipsa

Keywords

Single cell analysis, Lung metastasis, reactive capillary endothelial cells

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https://urn.fi/URN:NBN:fi:aalto-202512199504

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[kand] Sähkötekniikan korkeakoulu / ELEC