Abstract
Several origins have been proposed for cancer-associated fibroblasts (CAFs), including resident CD34+ stromal cells/telocytes (CD34+SCs/TCs). The characteristics and arrangement of mammary CD34+SCs/TCs are well known and invasive lobular carcinoma of the breast (ILC) is one of the few malignant epithelial tumours with stromal cells that can express CD34 or αSMA, which could facilitate tracking these cells. Our objective is to assess whether tissue-resident CD34+SCs/TCs participate in the origin of CAFs in ILCs. For this purpose, using conventional and immunohistochemical procedures, we studied stromal cells in ILCs (n:42) and in normal breasts (n:6, also using electron microscopy). The results showed (a) the presence of anti-CD34+ or anti-αSMA+ stromal cells in varying proportion (from very rare in one of the markers to balanced) around nests/strands of neoplastic cells, (b) a similar arrangement and location of stromal cells in ILC to CD34+SCs/TCs in the normal breast, (c) both types of stromal cells coinciding around the same nest of neoplastic cells and (d) the coexpression of CD34 and αSMA in stromal cells in ILC. In conclusion, our findings support the hypothesis that resident CD34+SCs/TCs participate as an important source of CAFs in ILC. Further studies are required in this regard in other tumours.
Highlights
CD34+ stromal cells (CD34+SCs) are present in the connective tissue of most organs
CD34+SCs/TCs are not observed in the stroma of numerous malignant invasive epithelial tumours, where they are replaced by αSMA+ stromal cells [9,10,11,12,13,14,15,16,17,18,19,20,21,22]
We explored invasive lobular carcinomas of the breast to determine the following: (a) whether the pattern of arrangement and location of tumoral stromal cells (CD34+ and αSMA+ stromal cells) in the tumours coincide with the arrangement and location of CD34+SCs/TCs in the normal breast, (b) whether both types of stromal cells are seen around the same nest of neoplastic cells or even around a single neoplastic cell and, more importantly, (c) whether stromal cells co-expressing CD34 and αSMA are present around neoplastic cells in the tumours
Summary
CD34+ stromal cells (CD34+SCs) are present in the connective tissue of most organs. A new cellular type, identified by electron microscopy and named telocyte (TC) [1,2] largely corresponds to the CD34+SCs observed in light microscopy (CD34+SCs/TCs) [1,3,4,5].These cells show a small body and long cytoplasmic processes (telopodes), in which a velamentous morphology has been observed in 3D imaging by FIB-SEM tomography [6,7,8].CD34+SCs/TCs are not observed in the stroma of numerous malignant invasive epithelial tumours, where they are replaced by αSMA+ stromal cells (myofibroblasts, cancerassociated fibroblasts: CAFs) [9,10,11,12,13,14,15,16,17,18,19,20,21,22]. Several origins have been proposed for CAFs, including tissue-resident CD34+SCs/TCs, bone marrow derived fibrocytes, pericytes and other possible precursor cells, such as endothelial cells (ECs), smooth muscle cells, adipocytes, and epithelial cells, to which the ability to transition or transdifferentiate has been attributed [23,24,25,26,27,28,29]. Among these cells, the participation of tissue-resident CD34+SCs/TCs as precursors of CAFs is very likely, as the process requiring the cellular loss of CD34 expression and the gain of αSMA expression
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