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Telomere-Associated Changes in Nuclear Architecture of Cancer-Associated Macrophage-like Cells in Liquid Biopsies
Aline Rangel-Pozzo1, Janine Wechsler2, Jessica Groult2
1CancerCare Manitoba Research Institute, University of Manitoba, Winnipeg, MB R3C 2B1, Canada.
Abstract:
During phagocytosis, tumor-associated macrophages (TAMs) can incorporate genetic material from tumor cells. The incorporation of extra genetic material may be responsible for advanced malignant behavior observed in some TAMs, making TAMs potentially important players in cancer progression. More recently, similar cells were described in the blood as cancer-associated macrophage-like cells (CAMLs). CAMLs may be equivalent to TAMs cells in the blood, and they express macrophage markers. However, their origin is still unclear. In a previous study, we showed for the first time the distinct telomere 3D structure of circulating tumor cells (CTCs) in melanoma and other cancers. In the present pilot study, we investigated, comparatively, the 3D telomere structure of CAMLs, CTCs and leucocytes from nine melanoma patients with metastatic cutaneous melanoma stage IV. CTC capture was performed by size-based filtration followed by cytological and immunocytological evaluation. Three-dimensional Quantitative Fluorescent in situ Hybridization was performed to measure differences in five 3D telomere parameters. Telomere parameters, such as number, length, telomere aggregates, nuclear volume, and a/c ratio, were compared among different cellular types (CTCs, CAMLs, and normal leucocytes). Three telomere parameters were significantly different between CAMLs and leucocytes. The combination of two telomere parameters (telomere length against the number of telomeres) resulted in the identification of two CAMLs subpopulations with different levels of genomic instability. Those populations were classified as profile 1 and 2. Profile 2, characterized by a high number of short telomeres, was observed in four of the nine melanoma patients. To our knowledge, this is the first pilot study to investigate 3D telomere parameters as hallmarks of nuclear architecture in CAMLs' population in comparison to leucocytes from the same patient. Further studies involving a larger patient sample size are necessary to validate these findings and explore their potential prognostic value.
Insights
Cancer-associated macrophage-like cells (CAMLs) in melanoma patients exhibit distinct 3D telomere structures compared to normal leucocytes. These differences may indicate genomic instability and potential prognostic value.
Area of Science:
- Oncology
- Cell Biology
- Genomics
Background:
- Tumor-associated macrophages (TAMs) can acquire genetic material from tumor cells, potentially driving cancer progression.
- Cancer-associated macrophage-like cells (CAMLs) found in the blood may be circulating counterparts of TAMs, but their origin and characteristics are unclear.
- Previous research identified distinct 3D telomere structures in circulating tumor cells (CTCs).
Purpose of the Study:
- To comparatively investigate the 3D telomere structure of CAMLs, CTCs, and leucocytes in melanoma patients.
- To identify potential nuclear architecture hallmarks in CAMLs using 3D telomere parameters.
Main Methods:
- Pilot study involving nine patients with stage IV metastatic cutaneous melanoma.
- Circulating tumor cells (CTCs) captured via size-based filtration.
- Three-dimensional Quantitative Fluorescent in situ Hybridization (3D-qFISH) to analyze telomere parameters (number, length, aggregates, nuclear volume, a/c ratio) in CAMLs, CTCs, and leucocytes.
Main Results:
- Significant differences in three telomere parameters were observed between CAMLs and leucocytes.
- Two CAML subpopulations with varying genomic instability were identified based on telomere length and number.
- Profile 2, characterized by numerous short telomeres, was found in four out of nine patients.
Conclusions:
- This is the first pilot study to analyze 3D telomere parameters in CAMLs compared to leucocytes.
- Distinct 3D telomere structures in CAMLs may serve as indicators of genomic instability.
- Further research with larger sample sizes is needed to validate findings and assess prognostic potential.
