Although cancer cells produce many factors that support their own proliferation and survival, it has been difficult to identify stromal factors that contribute to tumour progression. Sangaletti et al. show that stromal cells produce a secreted protein, acidic and rich in cysteine — Sparc — that helps organize the basement-membrane structure that is required for tumour progression.

Sparc is involved in tissue repair and remodelling, as it binds to components of the extracellular matrix such as fibrillar collagen and collagen type IV. It is expressed by various tumour and stromal cells, so Sangaletti et al. set out to learn more about its function. Mammary carcinoma cells that express high levels of Sparc grow into solid tumours in wild-type mice. These tumours have a well-structured stroma that comprises collagen type IV. In Sparc-null mice, however, the same tumours grew much more slowly. Tumours were smaller and less vascularized, contained necrotic areas and were devoid of collagen-type-IV-positive structures such as basement membranes of tumour lobules and blood vessels. So, Sparc production by the tumour environment, rather than the cancer cells themselves, is required for tumour progression.

But what host cells produce Sparc? Sangaletti et al. showed that when Sparc-expressing bone-marrow cells were transplanted into the null mice, tumours grew at the same rate as they did in wild-type mice. The transplanted bone-marrow-derived leukocytes localized to the tumours, where they expressed Sparc, allowing the tumour to develop a well-organized stromal compartment.

The authors propose that lack of Sparc production in the tumour environment prevents proper basement-membrane assembly, disrupting not only angiogenesis, but also removing a stromal 'shield' that protects the tumour from immune-cell infiltration.