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Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma. Transmission electron microscope (TEM)
Mihaela Gherghiceanu1, L M Popescu
1Victor Babeş National Institute of Pathology, Bucharest, Romania.
Insights
Interstitial cells of Cajal (ICLC) are confirmed in human mammary gland stroma using transmission electron microscopy (TEM). These cells exhibit specific ultrastructural features, supporting their role in mammary gland function.
Area of Science:
- Cell Biology
- Histology
- Oncology
Background:
- Interstitial cells of Cajal (ICLC) were previously identified in human mammary gland stroma using vital staining and immunochemistry.
- In vitro studies characterized the phenotype of these ICLC.
- Identification of ICLC outside the gastrointestinal tract necessitates transmission electron microscopy (TEM).
Purpose of the Study:
- To provide unequivocal evidence for the presence of ICLC in the intralobular stroma of the human resting mammary gland.
- To characterize the ultrastructural features of ICLC in the mammary gland using TEM based on established criteria.
Main Methods:
- Transmission electron microscopy (TEM) was employed to examine ICLC in the human mammary gland stroma.
- The 'platinum standard' of 10 TEM criteria was used for definitive ICLC diagnosis.
- Detailed analysis of cellular morphology, including caveolae, mitochondria, endoplasmic reticulum, cytoskeleton, and cytoplasmic processes.
Main Results:
- Unequivocal evidence for ICLC presence in the intralobular stroma was established via TEM.
- ICLC were located in the non-epithelial space among tubulo-alveolar structures.
- Characteristic features included specific percentages of cell volume for organelles, presence of filaments, occasional basal lamina and gap junctions, close contacts with nerve fibers and capillaries, and complex cytoplasmic processes.
Conclusions:
- The study confirms the existence of ICLC in the human mammary gland stroma through rigorous TEM analysis.
- The identified ultrastructural characteristics align with the 'platinum standard' for ICLC diagnosis.
- Further research is needed to elucidate the specific roles of ICLC in mammary gland homeostasis and pathology.
Abstract:
We have previously shown the existence of ICLC in human resting mammary gland stroma by means of methylene blue (vital) staining and c-kit immunopositivity (immunofluorescence and immunohistochemistry). In addition, we reported the phenotype characteristics of these ICLC in vitro (primary cell cultures). Since the identification of ICLC outside the gut requires, at this moment, the obligatory use of TEM, we used this technique and provide unequivocal evidence for the presence of ICLC in the intralobular stroma of human resting mammary gland. According to the 'platinum standard' (10 TEM criteria for the certitude diagnosis of ICLC), we found interstitial cells with the following characteristics: 1. location: among the tubulo-alveolar structures, in the non-epithelial space; 2. caveolae: approximately 2.5% of cell volume; 3. mitochondria: approximately 10% of cell volume; 4. endoplasmic reticulum: either smooth or rough, approximately 2-3% of cell volume; 5. cytoskeleton: intermediate and thin filaments, as well as microtubules are present; 6. myosin thick filaments: undetectable; 7. basal lamina: occasionally found; 8. gap junctions: occasionally found; 9. close contacts with targets: nerve fibers, capillaries, immunoreactive cells by 'stromal synapses'; 10. characteristic cytoplasmic processes: i) number: frequently 2-3; ii) length: several tens of mum; iii) thickness: uneven caliber, 0.1-0.5 microm, with dilations, but very thin from the emerging point; iv) aspect: moniliform, usually with mitochondria located in dilations; v) branching: dichotomous pattern; vi) Ca(2+) release units: are present; vii) network labyrinthic system: overlapping cytoplasmic processes. It remains to be established which of the possible roles that we previously suggested for ICLC (e.g. juxta- and/or paracrine secretion, uncommited progenitor cells, immunological surveillance, intercellular signaling, etc.) are essential for the epithelium/stroma equilibrium in the mammary gland under normal or pathological conditions.
