SNO cells: a novel tool for isolation of cancer stem cells as well as for identification of state of pre-metastatic niche

The Haematopoietic stem cells (HSC) are a subset of bone marrow cells that are responsible for the constant renewal of blood as well as capacity to generate daughter stem cells through self-renewal process by interacting with their specific microenvironments known as HSC niche.

Within the HSC niche in adult bone marrow, there is highly reciprocal relationship between osteoblasts (care for osteogenesis) and haematopoietic cells (care for haematopoiesis). HSCs interact not only with osteoblasts and its subsets (named osteoblastic niche) but also with other stromal cells, including sinusoidal endothelial cells (also named vascular niche).These osteoblastic niche and the vascular niche likely play role of maintaining a quiescent HSC microenvironment as well as regulating stem cell proliferation, differentiation and mobilization, respectively (1).

Recently Jiwang Zhang etal demonstrated that bone surface lining specialised cells called mononuclear spindle – shaped N-cadherin+ CD45- osteoblastic (SNO) cells, a subset of osteoblasts, is function as a crucial component of the HSC niche to support the long-term quiescent Haematopoietic stem cells (HSCs) (2). The osteoblastic niche not only maintains the quiescent stem-cells, but also promotes cancer metastasis (3) as well as likely retains mutant stem cells (4). Interestingly the SNO cells supporting the HSCs something like cleft form by b-integrin and N-cadherin.

In parallel, Kaplan etal have demonstrated a novel concept of pre-metastatic niche where prior to the arrival of tumor cells, tumour cells instruct bone marrow cells to migrate to the appropriate organ site and forming a receptive environment (or a pre-metastatic niche) for the tumour cells to occupy(5).

While integrating the date of quiescent cells are not completely quiescent, as they will be engaged into the cell cycle to take part physiological or pathological process (6), express a different profile of targets (7) as well as possible role of unknown molecular signaling pathways and microenvironmental ‘education’ for future metastatic progression (8), seems like further experimentation strategy might support the SNO cells may not only act as a novel tool for isolation of cancer stem cells but could also play supportive role for beginning of future metastatic progression. Moreover, evaluating the role of metastatic based signalling / secreted factors on the SNO cell complex may also gives exciting opportunity towards develop novel therapeutic target.




Relevant references:


(i) Tong Yin etal The stem cell niches in bone J Clin Invest. 2006 May; 116(5):1195-201.


(2) Jiwang Zhang etal Identification of the haematopoietic stem cell niche and control of the niche size Nature. 2003 Oct 23; 425(6960):836-41


(3) Mei Zhang etal Stem cells in the etiology and treatment of cancer Curr Opin Genet Dev. 2006 Feb; 16(1):60-4. Epub 2005 Dec 27.


(4) Anne Wilson etal c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation Genes Dev. 2004 Nov 15; 18(22):2747-63


(5) Rosandra N. Kaplan etal VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche Nature. 2005 Dec 8; 438(7069):820-7.


(6) Hong-Bo Zhang etal Identification of label-retaining cells in nasopharyngeal epithelia and nasopharyngeal carcinoma tissues Histochem Cell Biol. 2007 Mar; 127(3):347-54. Epub 2006 Nov 30


(7) Axel Schulenburg etal Neoplastic stem cells: a novel therapeutic target in clinical oncology Cancer. 2006 Nov 15; 107(10):2512-20


(8) Bethan Psaila etal Priming the 'soil' for breast cancer metastasis: the pre-metastatic niche Breast Dis. 2006-2007; 26:65-74

While learning got an idea to develop a hypothetical article..

Last week while reading some papers from stem-cell niche, irresistibly the atmospheres were helped me to develop a hypothetical article. Initially I had a thought to sent the preparation to one of academic professor and publish in a hypothetical journal; but due to some circumstances I could not able to do that at this moment. So here is the preparation (And, please note: this is an un-proofed copy).

I am not sure- whether this preparation might meets the standard of a hypothetical article or just plainly a kind of ‘stupid’ article. While preparing for this paper, however, the atmospheres are highly helped me to read and have some interdisciplinary knowledge on the emerging areas such as metastatic niche, cancer stem cells.

Picking up the area…

In order to have an overview on the field of stem-cell biology, I have found about 147947 references on the web site, Entrez while typing the key word stem-cells.

My initial thought is that I am going to walk in between a mountain. But once I have started to read few pages of the abstracts, immensely its guided me to have some idea and ignited me to start to read from the area of ‘stem-cell niche’ or microenvironment because of their remarkable cellular / physiological functions. Such as

- Acting as ‘specific anatomic locations’ that regulate tissue generation, maintenance and repair,

- ‘saves stem cells’ from depletion, while protecting the host from over-exuberant stem-cell proliferation,

- ‘acting as a reservoir’ for residual (cancer) stem / quiescent cells followed by opportunities to design stem-cell therapeutics, as well as

- ‘An associated steps’ for further cellular process such as self renewal and differentiation.

(did I miss any points here..?)