**1. Introduction**

The bone marrow (BM) consists of multilineage cell types, most especially the haematopoietic and mesenchymal lineage. The interaction between the haematopoietic and mesenchymal cell lineages are crucial in the maintenance of haematopoiesis [1, 2]. As a result, BM is the major site of haematopoiesis, which is the lifelong process of blood cells formation. Within the BM microenvironment or stroma, the haematopoietic and mesenchymal progenitor cells give rise to different cells such as immune cells, osteoclasts endothelial cells, stromal cells (mesenchymal stromal cells; MSC) and nerve cells [1, 3].

These stromal cells are characterised *in vitro* by the International Society for Cellular Therapy (ISCT) by three main qualities; (i) ability to adhere to plastic in standard culture conditions; (ii) expression of CD105, CD73 and CD90 surface molecules but lack expression of CD45, CD34, CD14 or CD11b, CD79a, or CD19, and HLA-DR proteins; (iii) multilineage differentiation potential into osteoblasts, adipocytes, fibroblasts and chondroblasts [4–6]. These stromal cells offer haematopoietic support, immunomodulation, and bone remodelling via cell-to-cell contact and/or secretion of soluble factors.

During carcinogenesis, the BM stroma goes rogue and enables cancer cells to recruit supporting cells from the tissue stroma needed to promote critical steps in tumour formation and thus, constitute a vital cog of the tumour microenvironment (TME) [5–7]. These stromal cells are recruited into the TME via secretion of different biomolecular factors such as cytokines, extracellular vesicles (EVs), chemokines, and growth factors. These stromal cells play important roles in all steps of cancer metastasis such as extracellular matrix (ECM) remodelling, migration, invasion, intravasation, circulation, survival, extravasation, and colonisation of distant secondary tumour sites [8–10].

Metastasis refers to the process of dissemination of cancer cells from its point of origin (primary site) to a distant disconnected part of the body, forming macroscopic secondary foci which constitutes a metastatic cancer [11, 12]. Metastasis was coined from the two Greek prefixes "meta" (alteration or change) and "stasis" (an equilibrium state), to represent both a process and its outcome. Despite the advances in cancer treatment, evidence from clinical experience and biologic inferences, show that metastasis is responsible for about 90% of cancer morbidity and mortality, with over two-thirds (66.7%) of deaths originating from solid tumours [13]. Metastasis is one of the hallmarks of cancer have been shown to occur as a complex, sequential but interrelated cell-biological events called the invasion-metastasis cascade [14].

Depending on the tumour type, stromal cell composition within the tumour microenvironment often varies and usually includes mesenchymal stem/stromal cells, pericytes, fibroblasts, adipocytes, vascular endothelial cells, stellate cells, and immune cells such as macrophages, T-cells, and natural killer (NK) cells [15–17]. Once recruited, these stromal cells undergo tumoral education and transform into tumour stroma. These damaged stromal cells are also vulnerable to cancer aggression either via direct contact with each other, through gap junctions thereby resulting in transfer of material from stromal cells to cancer cells [9, 15–17]. These lead to promotion of tumour growth, angiogenesis, proliferation, invasion, metastasis and chemoresistance once recruited to the tumour microenvironment [18].
