Fetal haemopoiesis marking low-grade urinary bladder cancer

Abstract

Background: The immunohistochemical features of fetal haemoglobin cells and their distribution patterns in solid tumours, such as colorectal cancer and blastomas, suggest that fetal haemopoiesis may take place in these tumour tissues. These locally highly concentrated fetal haemoglobin (HbF) cells may promote tumour growth by providing a more efficient oxygen supply. Methods and results: Biomarkers of HbF were checked in transitional cell carcinoma (TCC) of the urinary bladder, assessing this as a new parameter for disease management. Fetal haemoglobin was immunohistochemically examined in tumours from 60 patients with TCC of the bladder. Fetal haemoglobin erythrocytes and erythroblasts were mainly clonally distributed in proliferating blood vessels and not mixed with normal haemoglobin erythrocytes. The proportion of such HbF blood vessels could reach more than half of the total number of vessels. There were often many HbF erythroblasts distributed in one-cell or two-cell capillaries and present as 5–15% of cells in multi-cell vessels. This suggests a local proliferation of HbF-cell progenitors. Fetal haemoglobin cells were prominently marking lower grades of tumours, as 76% ( n =21) of the patients with G1pTa were HbF+, whereas only 6.7% ( n =30) of the patients with G3pT1-pT2a were HbF+. Conclusion: Our results suggest that HbF, besides being a potential new marker for early tumour detection, might be an essential factor of early tumour development, as in fetal life. Inhibiting HbF upregulation may provide a therapeutic target for the inhibition of tumour growth.

Revisiting Cancer Stem Cells as the Origin of Cancer-Associated Cells in the Tumor Microenvironment: A Hypothetical View from the Potential of iPSCs

“…These results coincide with our results which showed the ability of CSCs converted from iPSCs to differentiate into endothelial cells with the ability of tube formation [123]. Regarding blood and immune cells, many studies have shown that polyploidy giant cancer cells with the expression of stemness markers can differentiate into myoepithelial, endothelial and erythroid cells with a marker of hemoglobin [185][186][187][188][189]. This is in particular interesting because the well-believed concept of the bone marrow origin of TAMs have considerably changed recently.…”

Fetal Hemoglobin Levels as Indicator of Frequency and Duration of Blood Donation

“…However, frequent and long term blood donations without giving enough time for cell recovery will likely have damaging effects. Long term adverse effects of frequent blood donation like refractoriness of the bone marrow cells, which leads to anemia and anemic heart failure, may be the same features seen in some cancer cases where increased HbF levels were also observed (Rautonen and Siimes, 1990;Wolk et al, 2006;Wolk et al, 2007;Wolk and Martin, 2012). Moreover, short term adverse effects like bruising, continuous bleeding, dizziness, lightheadedness and nausea, pain and physical weakness are constant experience, some of which are experienced even with first time donors.…”

Blood and Cancer: Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments

“…Hematopoietic cells in the TME can be differentiated by specific gene expression, as shown by Chifman et al by analyzing microarray expression datasets [90]. Regarding red blood cell hematopoiesis, the ability of cancer cells to generate blood cells positive for fetal hemoglobin (HbF) within solid tumors has been proven [91][92][93]. Fetal hemoglobin supplies the tumor with oxygen and supporting tumor growth.…”